The α7-nicotinic acetylcholine receptor mediates the sensitivity of gastric cancer cells to taxanes.
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.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of General Surgery, Department of Surgery, New Taipei Hospital, Taipei, Taiwan.
Chao-Chiang
CC
Tu
Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Chien-Yu
CY
Huang
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Wan-Li
WL
Cheng
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.|Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, 250 Wu-Xin Street, Taipei, 110, Taiwan.
Chin-Sheng
CS
Hung
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.|National Dermatology Center, Ulaanbaatar, Mongolia.
Batzorig
B
Uyanga
Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.|Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, 250 Wu-Xin Street, Taipei, 110, Taiwan.
Po-Li
PL
Wei
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. r5424012@tmu.edu.tw.|Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. r5424012@tmu.edu.tw.|Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. r5424012@tmu.edu.tw.|Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, 250 Wu-Xin Street, Taipei, 110, Taiwan. r5424012@tmu.edu.tw.
Yu-Jia
YJ
Chang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000502:physiology*
D000970:Antineoplastic Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D034741:RNA, Small Interfering; D043823:Taxoids; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000077143:Docetaxel; D017239:Paclitaxel
A7-nAChR; Anti-proliferative therapy; Gastric cancer; Taxane