[Effects of traditional Tibetan drug Liu Tea on proliferation and chemotherapeutic sensitivity of drug-resistant human gastric cancer cell BGC823/5-FU]

Zhongguo Zhong Yao Za Zhi. 2016 Feb;41(4):603-608. doi: 10.4268/cjcmm20160409.
[Article in Chinese]

Abstract

To investigate the effects of Liu Tea extracts(LTE) on proliferation, apoptosis and drug sensitivity of drug-resistant gastric cancer cell BGC823/5-FU. MTT assay was used to analyze effect of LTE on cell growth and sensitivity chemotherapeutic drugs, and synergistic effect of the combination of LTE with 5-FU on BGC823/5-FU cells. Combination index (CI) was calculated by CompuSyn. Cell apoptosis was measured by flow cytometry (FCM). Protein expressions of P-gp, Bcl-2, Bax and Caspase-3 (17KD) were detected by Western blot at different concentrations of LTE in BGC823/5-FU cells (100, 200, 400 mg•L⁻¹). The results showed that LTE had an inhibitory effect on growth of BGC823/5-FU cell in a dose-time-dependent manner and significantly reduced IC₅₀ of 5-FU, CDDP, PTX and ADM to BGC823/5-FU cells(P<0.05), indicating it could reverse tolerance of drug resistant cells to chemotherapeutic drugs, with reversion multiples of 2.35, 1.68, 1.96, 0.52. The combination of LTE with 5-FU had positive synergistic effect on the BGC-823 cell line. FCM assay suggested that LTE could induce BGC823/5-FU apoptosis. The apoptosis rate was up to 46.2% when the cells were treated with 800 mg•L⁻¹ LTE after 24 h(P<0.01). According to the protein detection results, with the increase in concentration of LTE, the protein expression of Bcl-2 was gradually decreased(P<0.01), the expression of Bax and Caspase-3 were extremely increased(P<0.01), with statistical significance in difference(P<0.01) but no difference in the expression of P-gp between experiment group and control group. LTE can inhibit the growth of drug-resistant human gastric cancer cell BGC823/5-FU and reverse its chemotherapeutic tolerance to some extent. Inhibition of antiapoptotic proteins, activation of proapoptotic proteins and induction of apoptosis of resistant cells may be its main mechanisms.

Keywords: BGC823/5-FU cell line; apoptosis; gastric cancer; multidrug resistance; traditional Tibetan drug Liu Tea.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drugs, Chinese Herbal / pharmacology*
  • Fluorouracil / pharmacology
  • Humans
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / physiopathology*
  • Tibet

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Drugs, Chinese Herbal
  • CASP3 protein, human
  • Caspase 3
  • Fluorouracil