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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4421-4428
JournalTumor Biology
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Taxoids
Nicotinic Receptors
Stomach Neoplasms
Paclitaxel
docetaxel
Disease-Free Survival
Cell Cycle
Therapeutics
Poly(ADP-ribose) Polymerases
Small Interfering RNA
Cell Movement
Biomarkers
Cell Proliferation

Keywords

  • A7-nAChR
  • Anti-proliferative therapy
  • Gastric cancer
  • Taxane

ASJC Scopus subject areas

  • Cancer Research

Cite this

The α7-nicotinic acetylcholine receptor mediates the sensitivity of gastric cancer cells to taxanes. / Tu, Chao Chiang; Huang, Chien Yu; Cheng, Wan Li; Hung, Chin Sheng; Uyanga, Batzorig; Wei, Po Li; Chang, Yu Jia.

In: Tumor Biology, Vol. 37, No. 4, 01.04.2016, p. 4421-4428.

Research output: Contribution to journalArticle

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