Abstract
Objective
To observe the effects of oxaliplatin(L-OHP) on proliferation of human hepatoma cell line QGY in vitro and to investigate the mechanism.
Methods
The inhibition of proliferation in QGY cell was assayed by MTT-test. Morphologic changes were observed under light microscope and electronic microscope. Distribution of cell cycle and apoptosis were analyzed using flow cytometry. The expressions of cell cycle proteins and apoptosis-associated proteins were detected with immuno-histochemical technique.
Results
Oxaliplatin could inhibit the proliferation of QGY cells and the inhibition depended on the exposure time and dose. The cells showed morphologic changes of the early stage of apoptosis under the light microscope: the shrunk round cells, condensed cytoplasma and pycnosis of nucleus. Apoptotic cells and apoptotic body could be found under the transmission electronic microscope. The analysis of cell cycle indicated that oxaliplatin blocked cells at S and G2/M phases and the cells of G0/Gl phase reduced. When treated with oxaliplatin for 72h, the expressions of cyclin A and Bax were up-regulated, mutant type P53, Bcl-2 and Myc were down-regulated, and Fas was not changed.
Conclusion
Oxaliplatin could inhibit the proliferation of the hepatoma cell lines. Cells were blocked at S and G2/M phases. The apoptosis was related to the up-regulation of Bax and down-regulation of mutant type P53, Bcl-2 and Myc. Oxaliplatin could not induce apoptosis through the Fas pathway.
Similar content being viewed by others
References
Li L, Ahmed B, Mehta K, et al. Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer[J]. Mol Cancer Ther 2007; 6:1276–1282.
Mercalli A, Sordi V, Formicola R, et al. A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer[J]. Br J Cancer 2007; 96:1358–1367.
Benzina S, Debomy F, Bergerat JP, et al. The cytotoxicity of high-linear energy transfer radiation is reinforced by oxaliplatin in human glioblastoma cells[J]. Cancer Lett 2007; 254: 54–62.
Gu J, Yamamoto H, Lu X, et al. Low-dose oxaliplatin enhances the antitumor efficacy of paclitaxel in human gastric cancer cell lines[J]. Digestion 2006; 74:19–27.
William-Faltaos S, Rouillard D, Lechat P, et al. Cell cycle arrest and apoptosis induced by oxaliplatin (L-OHP) on four human cancer cell lines[J]. Anticancer Res 2006; 26: 2093–2099.
El-Salhy M, Hilding L, Royson H, et al. Comparison between triple therapy with octreotide, galanin and serotonin vs. irinotecan or oxaliplatin in combination with 5-fluorouracil/leukovorin in human colon cancer[J]. Int J Oncol 2005; 27: 687–691.
Tang WX, Luo YP, Wang RX. Establishment of MTT assay on anti-cancer drug sensitivity with human solid tumors[J]. J Chongqing Univ Med Sci(in Chin) 1992; 17: 103–108.
Chou TC, Talalay P. Quantitative analysis of dose-effects relationships: the combined effects of multiple drugs on enzyme inhibitors[J]. Adv Enzyme Regul 1984; 22: 27–30.
Harrington DJ, lessey BA, Raiv, et al. Tenascin is differentially expressed in endometrium and endometriosis[J]. J Pathol 1999; 187: 242–248.
Sayeed A, Konduri SD, Liu W, et al. Estrogen receptor alpha inhibits p53-mediated transcriptional repression: implications for the regulation of apoptosis[J]. Cancer Res 2007; 67:7746–7755.
Ozaki T, Li Y, Kikuchi H, et al. The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis[J]. Biochem Biophys Res Commun 2006; 351: 57–63.
Jin YJ, Wang J, Qiao C, et al. A novel mechanism for p53 to regulate its target gene ECK in signaling apoptosis[J]. Mol Cancer Res 2006; 4: 769–778.
Yu Z, Shah DM. Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells[J]. Gynecol Oncol 2007; 106: 541–548.
Pessina A, Croera C, Savalli N, et al. Bcl-2 down modulation in WEHI-3B/CTRES cells resistant to Cholera Toxin (CT)-induced apoptosis[J]. Cell Res 2006; 16: 306–312.
Peng LM, Wang ZL. Basic and clinical aspects of apoptosis[M]. Beijing: People’s Health Publishing House, 2000; 2–9
Yang LJ, Wang WL, Si XH. Induction by ethanol of hepatocellular carcinoma cell HCC-9204 apoptosis and the involvement of Bax and Bcl-2 proteins[J]. J Cell Mol Immunol 2001; 17: 315–317.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by the key program for the Science & Tchnology Research of Health Bureau of Chongqing Municipality (No. 200101-1-018).
Rights and permissions
About this article
Cite this article
He, S., Zuo, Gq., Zhang, Y. et al. Mechanism of suppression on proliferation of QGY cell by oxaliplatin. Chin. J. Cancer Res. 19, 263–268 (2007). https://doi.org/10.1007/s11670-007-0263-6
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11670-007-0263-6