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Tumor Biology

, Volume 37, Issue 4, pp 4421–4428 | Cite as

The α7-nicotinic acetylcholine receptor mediates the sensitivity of gastric cancer cells to taxanes

  • Chao-Chiang Tu
  • Chien-Yu Huang
  • Wan-Li Cheng
  • Chin-Sheng Hung
  • Batzorig Uyanga
  • Po-Li Wei
  • Yu-Jia Chang
Original Article

Abstract

Gastric cancer is difficult to cure because most patients are diagnosed at an advanced disease stage. Systemic chemotherapy remains an important therapy for gastric cancer, but both progression-free survival and disease-free survival associated with various combination regimens are limited because of refractoriness and chemoresistance. Accumulating evidence has revealed that the homomeric α7-nicotinic acetylcholine receptor (A7-nAChR) promotes human gastric cancer by driving cancer cell proliferation, migration, and metastasis. Therefore, A7-nAChR may serve as a potential therapeutic target for gastric cancer. However, the role of A7-nAChR in taxane therapy for gastric cancer was unclear. Cells were subjected to A7-nAChR knockdown (A7-nAChR KD) using short interfering RNA (siRNA). The anti-proliferative effects of taxane were assessed via 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase–mediated nick-end labeling (TUNEL), and cell cycle distribution assays. A7-nAChR-KD cells exhibited low resistance to docetaxel and paclitaxel treatment, as measured by the MTT assay. Following paclitaxel treatment, the proportion of apoptotic cells was higher among A7-nAChR-KD cells than among scrambled control cells, as measured by cell cycle distribution and TUNEL assays. Further molecular analyses showed a reduction in the pAKT levels and a dramatic increase in the Bad levels in paclitaxel-treated A7-nAChR-KD cells but not in scrambled control cells. Following paclitaxel treatment, the level of Bax was slightly increased in both cell populations, whereas Poly (ADP-ribose) polymerase (PARP) cleavage was increased only in A7-nAChR-KD cells. These findings indicate that A7-nAChR-KD cells are more sensitive to paclitaxel treatment. We conclude that A7-nAChR may be a key biomarker for assessing the chemosensitivity of gastric cancer cells to taxane.

Keywords

A7-nAChR Gastric cancer Anti-proliferative therapy Taxane 

Abbreviations

α7-nAChR

Alpha-7 nicotinic acetylcholine receptor

PARP

Poly (ADP-ribose) polymerase

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PI

Propidium iodide

TUNEL

Terminal deoxynucleotidyl transferase dUTP nick end labeling

Notes

Acknowledgments

This work was supported by a grant from the National Science Council of Taiwan (Grant No. NSC101-2314-B-038-016-MY3).

Compliance with ethical standards

Conflicts of interest

None

Author contributions

Conception or design of the study: CC Tu, CY Huang, CS Hung, PL Wei, YJ Chang

Experimental design: CY Huang, CS Hung, YJ Chang

Drafting of the manuscript: CC Tu, CY Huang, WL Cheng, YJ Chang

Acquisition, analysis, or interpretation of data for the study: CY Huang, WL Cheng, B Uyanga, YJ Chang

Final approval of the version to be published: CC Tu, CY Huang, PL Wei, YJ Chang

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Chao-Chiang Tu
    • 1
    • 2
  • Chien-Yu Huang
    • 3
  • Wan-Li Cheng
    • 1
  • Chin-Sheng Hung
    • 6
    • 7
    • 8
  • Batzorig Uyanga
    • 1
    • 4
    • 9
  • Po-Li Wei
    • 5
    • 6
    • 7
    • 8
  • Yu-Jia Chang
    • 1
    • 6
    • 7
    • 8
  1. 1.Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  2. 2.Division of General Surgery, Department of SurgeryNew Taipei HospitalTaipeiTaiwan
  3. 3.Division of General Surgery, Department of Surgery, Shuang Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  4. 4.Mongolian National University of Medical SciencesUlaanbaatarMongolia
  5. 5.Graduate Institute of Cancer Biology and Drug DiscoveryTaipei Medical UniversityTaipeiTaiwan
  6. 6.Department of Surgery, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  7. 7.Division of General Surgery, Department of Surgery, Taipei Medical University HospitalTaipei Medical UniversityTaipeiTaiwan
  8. 8.Cancer Research Center, Taipei Medical University HospitalTaipei Medical UniversityTaipeiTaiwan
  9. 9.National Dermatology CenterUlaanbaatarMongolia

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