Sensitivity of gastric cancer stem cells to 5-fluorouracil and biological mechanism underlying multidrug resistance

doi:10.3969/j.issn.2095-4344.2015.19.012

Abstract

Abstract:

BACKGROUND: Fluorouracil is a basic chemotherapy drug for gastric cancer, and its drug resistance is commonly seen in clinic. Cancer stem cells have low sensitivity to chemotherapy drugs, which may be an important cause of tumor recurrence and progression following chemotherpay.
OBJECTIVE: To explore the sensitivity of gastric cancer stem cells to 5-fluorouracil and related biology mechanism underlying multidrug resistance.
METHODS: Stem cell marker CD44 and multidrug resistance protein thymidylate synthase in 69 cases of gastric cancer tissues were tested by immunohistochemical staining. The selection strategy was based on the clonal morphology, and gastric cancer stem cells were isolated from human gastric cancer cell line AGS to detect the expression of CD44 and thymidylate synthase and the self renewing ability. Inhibitory concentration 50 (IC50) of 5-fluorouracil in different AGS cell clone was detected using cell counting kit-8.
RESULTS AND CONCLUSION: In 69 cases of gastric cancer tissues, the positive expression rates of thymidylate synthase and CD44 were 57% (39/69) and 61% (42/69), respectively, and there was a positive correlation between the expression of CD44 and thymidylate synthase (Kappa=0.41, χ²=11.59, P < 0.05). Cloning efficiency of the AGS cell line was 39% (29/69), wherein, vice cloning, secondary cloning, and full clone proportions were 17% (5/29), 69% (20/29), 14% (4/29), respectively. After sub-cloning, the clone was digested using trysin followed by low-density passage; vice clones were unable to passage, secondary clones could only
passage a few, and full clones could serially passage. After treatment with different concentrations of 5-fluorouracil, the full clone growth inhibition rate was significantly lower than that of secondary clones and AGS cells (P < 0.05). These findings show that gastric cancer stem cells are less sensitive to 5-fluorouracil, indicating the cells have a resistance to chemotherapy drugs, which may be one of the chemotherapy resistance mechanisms in the clinical treatment of gastric cancer.

Key words: Stomach Neoplasms, Fluorouracil, Colony-Forming Units Assay

CLC Number:

R394.2

Le Xiong, Yang De-tong, Zhang Hong-hai . Sensitivity of gastric cancer stem cells to 5-fluorouracil and biological mechanism underlying multidrug resistance [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(19): 3022-3026.

Figures/Tables 1

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