Original Article
Programmed death 1 induces cell chemoresistance to 5-fluorouracil in gastric cancer cell lines
Abstract
Background: Gastric cancer is characterized by a high rate of relapse and failure of chemotherapy because of the emergence of drug resistant cells. Programmed death 1 (PD1) controls carcinogenesis in several human malignancies and could be involved in the resistance of cells to several chemotherapeutic agents. Herein, we analyzed the role of PD1 in the resistance of gastric cancer to 5-fluorouracil (5-FU).
Methods: PD1-expression vector or siRNA were used to analyze the functional effects of PD1 on chemoresistance of gastric cancer cells to 5-FU. PD1 expression, proliferation and apoptosis of gastric cancer cells were assayed by real-time PCR (RT-PCR), MTT and flow cytometry respectively. The effect of PD1 expression on ATP binding cassette subfamily C member 1 (ABCC1) and anti-apoptotic factor (Bcl-2) were also assayed by RT-PCR.
Results: Little expression of PD1 was observed in SGC7901 cells, while increased expression in 5-FU-resistant gastric cell line SGC7901/5-FU. Upregulated expression of PD1 in SGC7901 cells was identified to promote proliferation and 5-FU resistance and inhibit apoptosis, while downregulation of PD1 to inhibit 5-FU resistance and proliferation and induce apoptosis. When PD1 was overexpressed in SGC7901 cells, the protein levels of ABCC1 and Bcl-2 were up-regulated, while PD1 downregulation in SGC7901/5-FU cells significantly decreased the expression of ABCC1 and Bcl-2.
Conclusions: These results indicated that PD1 may influence the sensitivity of 5-FU treatment.
Methods: PD1-expression vector or siRNA were used to analyze the functional effects of PD1 on chemoresistance of gastric cancer cells to 5-FU. PD1 expression, proliferation and apoptosis of gastric cancer cells were assayed by real-time PCR (RT-PCR), MTT and flow cytometry respectively. The effect of PD1 expression on ATP binding cassette subfamily C member 1 (ABCC1) and anti-apoptotic factor (Bcl-2) were also assayed by RT-PCR.
Results: Little expression of PD1 was observed in SGC7901 cells, while increased expression in 5-FU-resistant gastric cell line SGC7901/5-FU. Upregulated expression of PD1 in SGC7901 cells was identified to promote proliferation and 5-FU resistance and inhibit apoptosis, while downregulation of PD1 to inhibit 5-FU resistance and proliferation and induce apoptosis. When PD1 was overexpressed in SGC7901 cells, the protein levels of ABCC1 and Bcl-2 were up-regulated, while PD1 downregulation in SGC7901/5-FU cells significantly decreased the expression of ABCC1 and Bcl-2.
Conclusions: These results indicated that PD1 may influence the sensitivity of 5-FU treatment.
