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| Mechanism research on apoptosis of hepatocellular carcinoma induced by sodium bicarbonate |
| ZHANG Yan1 QIAO Luxin2 ZENG Jing2 XU Jun1 SHI Ying2▲ |
1.Beijing Zhongguancun Middle School, Beijing 100086, China;
2.Beijing You′an Hospital, Capital Medical University Beijing Institute of Hepatology, Beijing 100069, China |
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Abstract Objective To explore the apoptotic mechanism of hepatocellular carcinoma (HCC) induced by sodium bicarbonate (SB). Methods HepG2 cells were implanted the subcutaneous of 5 athymic mice (7-week age) to form hepatocarcinoma mouse model and the growth and necrosis of hepatocellular carcinoma was observed under the condition of local mass injection of 5% SB. The apoptosis of hepatocellular carcinoma cell line HepG2 was observed by Calcein/PI staining and flow cytometry at SB exposure and different pH gradients. The expression of Bax/bcl2 were also detected in HepG2 cells under SB exposure by real-time PCR and western blotting. Results Animal in vivo studies revealed that 5% SB local injection for 4 weeks could inhibit tumor growth and cause tumor necrosis in 3 of 5 hepatocarcinoma mice. One hepatocarcinoma mice died and another mice had an enlarged tumor. 5% SB was diluted to the volume ratio 3/4, 1/2, 1/4, 1/8, 1/16 and negative control by DMEM and Calcein/PI staining in vitro showed that HepG2 apoptosis mice decreased in turn. Flow cytometry showed the similar results in 5% SB volume ratio: 1/2, 1/4, 1/8 and 1/16. The medium DMEM was titrated to pH6.0, pH6.25, pH6.5, pH6.75, pH7.0, pH7.25, pH7.5, pH7.75 and pH8.0. The lowest rate of HepG2 apoptosis was at pH7.0 and pH7.25. As the increasing of acidity or alkalinity, the apoptosis rate of HepG2 increased gradually. Flow cytometry also showed the similar results. Compared with control, Bax mRNA and protein expression in SB exposed HepG2 cell were not changed, but bcl2 mRNA and protein expression were decreased. Conclusion SB can induce HCC apoptosis by changing the internal environmental pH and inhibiting the expression of apoptotic protein blc2.
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