Skip to main content

Advertisement

SpringerLink
Log in

Prospective Antitumor Effects of the Combination of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and Cisplatin Against Esophageal Squamous Cell Carcinoma

  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which binds to death receptor (DR) 4 and DR5 to mediate apoptosis. Previously, we showed that the combination of TRAIL and cisplatin was effective against esophageal squamous cell carcinoma (ESCC) cell lines in vitro and in vivo, using one of the ESCC cell lines (KYSE 170). KYSE 110 is another ESCC cell line, but it lacks expression of decoy receptors. Thus, by using KYSE 110, we can eliminate any effects from two decoy receptors.

Methods

We used reverse transcription–polymerase chain reaction (RT-PCR) to reveal the expression of TRAIL receptors. Crystal violet staining and flow cytometry were done to confirm cytotoxicity and induction of apoptosis. KYSE 110 xenografted in nude mice was treated with TRAIL and cisplatin. The tumors were subsequently removed for microscopic studies.

Results

ESCC sensitive to the combination treatment in vitro was also sensitive to the treatment in vivo. Furthermore, induction of apoptosis resulted via the caspase cascade and the mitochondrial pathway. Low doses of both cisplatin and TRAIL sufficed to obtain these effects.

Conclusion

These findings imply that in clinical application, low doses of both agents could be administered to minimize side effects, while augmenting tumoricidal activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. M Imamura Y Shimada Y Kanda M Fukumoto K Yanagibashi T Miyahara et al. (1992) ArticleTitleUsefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer Surgery Today 22 409–15 Occurrence Handle1421861 Occurrence Handle1:STN:280:DyaK3s%2Fktl2lsA%3D%3D Occurrence Handle10.1007/BF00308789

    Article  PubMed  CAS  Google Scholar 

  2. RS Wiley K Schooley PJ Smolak WS Din C-P Huang JK Nicholl et al. (1995) ArticleTitleIdentification and characterization of a new member of the TNF family that induces apoptosis Immunity 3 673–82 Occurrence Handle8777713 Occurrence Handle1:CAS:528:DyaK28XhtF2iug%3D%3D Occurrence Handle10.1016/1074-7613(95)90057-8

    Article  PubMed  CAS  Google Scholar 

  3. RM Pitti SA Marsters S Ruppert CJ Donahue A Moore A Ashkenazi (1996) ArticleTitleInduction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family J Biol Chem 271 IssueID22 12687–90 Occurrence Handle8663110 Occurrence Handle1:CAS:528:DyaK28XjtlGjtrc%3D Occurrence Handle10.1074/jbc.271.22.12687

    Article  PubMed  CAS  Google Scholar 

  4. G Pan K O'Rourke AM Chinnaiyan R Gentz R Ebner J Ni et al. (1997) ArticleTitleThe receptor for the cytotoxic ligand TRAIL Science 276 111–3 Occurrence Handle9082980 Occurrence Handle1:CAS:528:DyaK2sXitl2jsL4%3D Occurrence Handle10.1126/science.276.5309.111

    Article  PubMed  CAS  Google Scholar 

  5. P Schneider JL Bodmer M Thome K Hofmann N Holler J Tschopp (1997) ArticleTitleCharacterization of two receptors for TRAIL FEBS Lett 416 329–34 Occurrence Handle9373179 Occurrence Handle1:CAS:528:DyaK2sXmvFWjsLc%3D Occurrence Handle10.1016/S0014-5793(97)01231-3

    Article  PubMed  CAS  Google Scholar 

  6. JP Sheridan SA Marsters RM Pitti A Gurney M Skubatch D Baldwin et al. (1997) ArticleTitleControl of TRAIL-induced apoptosis by a family of signaling and decoy receptors Science 277 818–21 Occurrence Handle9242611 Occurrence Handle1:CAS:528:DyaK2sXlt1eks78%3D Occurrence Handle10.1126/science.277.5327.818

    Article  PubMed  CAS  Google Scholar 

  7. G Pan J Ni Yu G-L Wei Y-F R Gentz VM Dixit (1997) ArticleTitleAn antagonist decoy receptor and a death domain-containing receptor for TRAIL Science 277 815–8 Occurrence Handle9242610 Occurrence Handle1:CAS:528:DyaK2sXlt1eksro%3D Occurrence Handle10.1126/science.277.5327.815

    Article  PubMed  CAS  Google Scholar 

  8. H Walczak MA Degli-Esposti RS Johnson PJ Smolak JY Waugh N Boiani et al. (1997) ArticleTitleTRAIL–R2: a novel apoptosis-mediating receptor for TRAIL EMBO J 16 IssueID17 5386–97 Occurrence Handle9311998 Occurrence Handle1:CAS:528:DyaK2sXmsVGlsLo%3D Occurrence Handle10.1093/emboj/16.17.5386

    Article  PubMed  CAS  Google Scholar 

  9. PM Chaundhary M Eby A Jasmin A Bookwalter J Murray L Hood (1997) ArticleTitleDeath receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kB pathway Immunity 7 821–30 Occurrence Handle10.1016/S1074-7613(00)80400-8

    Article  Google Scholar 

  10. SA Marsters JP Sheridan RM Pitti A Huang M Skubatch D Baldwin et al. (1997) ArticleTitleA novel receptor for Apo2L/TRAIL contains a truncated death domain Curr Biol 7 1003–6 Occurrence Handle9382840 Occurrence Handle1:CAS:528:DyaK2sXotFSls7o%3D Occurrence Handle10.1016/S0960-9822(06)00422-2

    Article  PubMed  CAS  Google Scholar 

  11. G Pan J Ni Yu G L Wei Y-F VM Dixit (1998) ArticleTitleTRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signaling FEBS Lett 424 41–5 Occurrence Handle9537512 Occurrence Handle1:CAS:528:DyaK1cXhsFeju78%3D Occurrence Handle10.1016/S0014-5793(98)00135-5

    Article  PubMed  CAS  Google Scholar 

  12. MA Degli-Esposti WC Dougall PJ Smolak JY Waugh CA Smith RG Goodwin (1997) ArticleTitleThe novel receptor TRAIL-R4 induces NF-kB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain Immunity 7 813–20 Occurrence Handle9430226 Occurrence Handle1:CAS:528:DyaK1cXjsFWgtQ%3D%3D Occurrence Handle10.1016/S1074-7613(00)80399-4

    Article  PubMed  CAS  Google Scholar 

  13. M Jo Seol D-W Kim T-H JE Esplen K Dorko TR Billiar et al. (2000) ArticleTitleApoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand Nat Med 6 IssueID5 564–7 Occurrence Handle10802713 Occurrence Handle1:CAS:528:DC%2BD3cXjtFyhtrk%3D Occurrence Handle10.1038/75045

    Article  PubMed  CAS  Google Scholar 

  14. K Kim MJ Fisher S-Q Xu WS El-Deiry (2000) ArticleTitleMolecular determinants of response to TRAIL in killing of normal and cancer cells Clin Cancer Res 6 335–46 Occurrence Handle10690508 Occurrence Handle1:CAS:528:DC%2BD3cXhs1aksLw%3D

    PubMed  CAS  Google Scholar 

  15. MM Keane SA Ettenberg MM Nau EK Russell S Lipkowitz (1999) ArticleTitleChemotherapy augments TRAIL-induced apoptosis in breast cell lines Cancer Res 59 734–41 Occurrence Handle9973225 Occurrence Handle1:CAS:528:DyaK1MXhtFSitLk%3D

    PubMed  CAS  Google Scholar 

  16. TS Griffith CT Rauch PJ Smolak JY Waugh N Boiani DH Lynch et al. (1999) ArticleTitleFunctional analysis of TRAIL receptors using monoclonal antibodies J Immunol 162 2597–605 Occurrence Handle10072501 Occurrence Handle1:CAS:528:DyaK1MXhtlOmtrc%3D

    PubMed  CAS  Google Scholar 

  17. M Leverkus M Neumann T Mengling CT Rauch E-B Brocker PH Krammer et al. (2000) ArticleTitleRegulation of tumor necrosis factor-related apoptosis-inducing ligand sensitivity in primary and transformed human keratinocytes Cancer Res 60 553–9 Occurrence Handle10676636 Occurrence Handle1:CAS:528:DC%2BD3cXht1Gmt7g%3D

    PubMed  CAS  Google Scholar 

  18. J-Z Qin V Chaturvedi B Bonish BJ Nickoloff (2001) ArticleTitleAvoiding premature apoptosis of normal epidermal cells Nat Med 7 IssueID4 385–6 Occurrence Handle11283637 Occurrence Handle1:CAS:528:DC%2BD3MXis1ymtbo%3D Occurrence Handle10.1038/86401

    Article  PubMed  CAS  Google Scholar 

  19. D Lawrence Z Shahrokh S Marsters K Achilles D Shih B Mounho et al. (2001) ArticleTitleDifferential hepatocyte toxicity of recombinant Apo2L/TRAIL versions Nat Med 7 IssueID4 383–5 Occurrence Handle11283636 Occurrence Handle1:CAS:528:DC%2BD3MXis1ymtb0%3D Occurrence Handle10.1038/86397

    Article  PubMed  CAS  Google Scholar 

  20. M Nagane G Pan JJ Weddle VM Dixit WK Cavenee H-J Su Huang (2000) ArticleTitleIncreased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo Cancer Res 60 847–53 Occurrence Handle10706092 Occurrence Handle1:CAS:528:DC%2BD3cXhs1Siu7w%3D

    PubMed  CAS  Google Scholar 

  21. A Eggert MA Grotzer TJ Zuzak BR Wiewrodt R Ho N Ikegaki et al. (2001) ArticleTitleResistance to Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression Cancer Res 61 1314–9 Occurrence Handle11245427 Occurrence Handle1:CAS:528:DC%2BD3MXhvVelsbk%3D

    PubMed  CAS  Google Scholar 

  22. T Naka K Sugamura BL Hylander MB Widmer YM Rustum EA Repasky (2002) ArticleTitleEffects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice Cancer Res 62 5800–6 Occurrence Handle12384541 Occurrence Handle1:CAS:528:DC%2BD38XotFyktrY%3D

    PubMed  CAS  Google Scholar 

  23. SB Gibson R Oyer AC Spalding SM Anderson GL Johnson (2000) ArticleTitleIncreased expression of death receptors 4 and 5 synergizes the apoptosis response to combined treatment with etoposide and TRAIL Mol Cell Biol 20 IssueID1 205–12 Occurrence Handle10594023 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Sr Occurrence Handle10.1128/MCB.20.1.205-212.2000

    Article  PubMed  CAS  Google Scholar 

  24. S Hopkins-Donaldson J-L Bodmer KB Bourloud CB Brognara J Tschopp et al. (2000) ArticleTitleLoss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis Cancer Res 60 4315–9 Occurrence Handle10969767 Occurrence Handle1:CAS:528:DC%2BD3cXmsVaitbs%3D

    PubMed  CAS  Google Scholar 

  25. K Kondo S Yamasaki T Sugie N Teratani T Kan M Imamura et al. (2006) ArticleTitleCisplatin-dependent upregulation of death receptors 4 and 5 augments induction of apoptosis by TNF-related apoptosis-inducing ligand against esophageal squamous cell carcinoma Int J Cancer 118 230–42 Occurrence Handle16003725 Occurrence Handle1:CAS:528:DC%2BD2MXht1KgsrvK Occurrence Handle10.1002/ijc.21283

    Article  PubMed  CAS  Google Scholar 

  26. Y Shimada M Imamura T Wagata N Yamaguchi T Tobe (1992) ArticleTitleCharacterization of 21 newly established esophageal cancer cell lines Cancer 69 277–84 Occurrence Handle1728357 Occurrence Handle1:STN:280:DyaK38%2Fps12mtw%3D%3D Occurrence Handle10.1002/1097-0142(19920115)69:2<277::AID-CNCR2820690202>3.0.CO;2-C

    Article  PubMed  CAS  Google Scholar 

  27. Y Kanda Y Nishiyama Y Shimada M Imamura H Nomura H Hiai et al. (1994) ArticleTitleAnalysis of gene amplification and overexpression in human esophageal-carcinoma cell lines Int J Cancer 58 291–7 Occurrence Handle7913084 Occurrence Handle1:CAS:528:DyaK2cXlslKns74%3D

    PubMed  CAS  Google Scholar 

  28. TS Griffith WA Chin GC Jackson DH Lynch MZ Kubin (1998) ArticleTitleIntracellular regulation of TRAIL-induced apoptosis in human melanoma cells J Immunol 161 2833–40 Occurrence Handle9743343 Occurrence Handle1:CAS:528:DyaK1cXmtVKgs74%3D

    PubMed  CAS  Google Scholar 

  29. A Suliman A Lam R Datta RK Strivastava (2001) ArticleTitleIntracellular mechanism of TRAIL. apoptosis through mitochondrial-dependent and -independent pathways Oncogene 20 2122–33 Occurrence Handle11360196 Occurrence Handle1:CAS:528:DC%2BD3MXjsVCht7c%3D Occurrence Handle10.1038/sj.onc.1204282

    Article  PubMed  CAS  Google Scholar 

  30. R Ravi A Bedi (2002) ArticleTitleRequirement of BAX for TRAIL/Apo2L-induced apoptosis of colorectal cancers: synergism with Sulindac-mediated inhibition of Bcl-XL Cancer Res 62 1583–7 Occurrence Handle11912124 Occurrence Handle1:CAS:528:DC%2BD38XisVSis7s%3D

    PubMed  CAS  Google Scholar 

  31. Kim Y-H Kim J-Y I Chang S Kim YK Pak B-H Oh et al. (2001) ArticleTitleResistance of mitochondrial DNA-deficient cells to TRAIL: role of Bax in TRAIL-induces apoptosis Oncogene 21 3139–48 Occurrence Handle10.1038/sj.onc.1205406

    Article  Google Scholar 

  32. M Sarker C Ruiz-Ruiz G Robledo A López-Rivas (2002) ArticleTitleStimulation of the mitogen-activated protein kinase pathway antagonizes TRAIL-induced apoptosis downstream of BID cleavage in human breast cancer MCF-7 cells Oncogene 21 4323–7 Occurrence Handle12082620 Occurrence Handle1:CAS:528:DC%2BD38XkslKmtL4%3D Occurrence Handle10.1038/sj.onc.1205523

    Article  PubMed  CAS  Google Scholar 

  33. KG Wolter Y-T Hsu CL Smith A Nechushtan X-G Xi RJ Youle (1997) ArticleTitleMovement of Bax from the cytosol to mitochondria during apoptosis J Cell Biol 139 IssueID5 1281–92 Occurrence Handle9382873 Occurrence Handle1:CAS:528:DyaK2sXnvFeqsLg%3D Occurrence Handle10.1083/jcb.139.5.1281

    Article  PubMed  CAS  Google Scholar 

  34. TR Singh S Shankar X Chen M Asim RK Strivastava (2003) ArticleTitleSynergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related Apoptosis-inducing Ligand/Apo-2L ligand on apoptosis and on regression of breast carcinoma in vivo Cancer Res 63 5390–400 Occurrence Handle14500373 Occurrence Handle1:CAS:528:DC%2BD3sXntlekurg%3D

    PubMed  CAS  Google Scholar 

  35. N Inoue S Yamasaki K Kondo T Kan K Furumoto M Imamura (2003) ArticleTitleDendritic cells coinjected with tumor cells treated with an anticancer drug to induce tumor rejection Surgery Today 33 269–76 Occurrence Handle12707821 Occurrence Handle1:CAS:528:DC%2BD3sXjtVehsrg%3D Occurrence Handle10.1007/s005950300060

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Kan Kondo, Naoki Teratani, Takatsugu Kan & Yutaka Shimada

  2. Department of Surgery, Murakami Memorial Hospital, Gifu, Japan

    Seiji Yamasaki

  3. Department of Surgery, Wakayama Red-cross Hospital, Wakayama, Japan

    Naoya Inoue

  4. Department of Surgery, Kyoto Police Hospital, Kyoto, Japan

    Tomoharu Sugie

  5. Department of Surgery, Japan Baptist Hospital, Kyoto, Japan

    Kan Kondo

Authors
  1. Kan Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seiji Yamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoya Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomoharu Sugie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoki Teratani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takatsugu Kan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yutaka Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kondo, K., Yamasaki, S., Inoue, N. et al. Prospective Antitumor Effects of the Combination of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and Cisplatin Against Esophageal Squamous Cell Carcinoma. Surg Today 36, 966–974 (2006). https://doi.org/10.1007/s00595-006-3295-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-006-3295-5

Key words

Search

Navigation