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| Effects of silymarin on HIF‑1α and MDR1 expression in HepG‑2 cells under hypoxia |
| Objective To investigate the effect of silymarin (SM) on the expression of hypoxia-inducible factor-1 alpha
(HIF?1α) and multidrug resistance 1 (MDR1) in HepG?2 cells under hypoxia. Methods After treatment of HepG?2 cells with
different concentrations of SM (0, 10, 20, 40 mg/L) and concentration gradient chemotherapeutic drugs (doxorubicin, sorafenib,
cisplatin), MTT assay was used to detect the effect of different concentrations of SM on the sensitivity of HepG?2 cells to
chemotherapeutic drugs. Under hypoxic conditions, HepG?2 cells were treated with SM at 0, 10, 20, and 40 mg/L for 8 h, RTPCR was used to detect the effects of different concentrations of SM on the expression levels of HIF?1α and MDR1 mRNA, and
Western Blot was used to detect the effects of different concentrations of SM on the protein expression levels of HIF?1α and Pglycoprotein (P?Gp) in HepG?2 cells. Results With the increase of SM concentration, the sensitivity of HepG?2 cells to the
chemotherapy drugs doxorubicin, sorafenib and cisplatin gradually increased. Compared with the control group, there was no
significant difference in HIF?1α mRNA expression in the 10, 20, and 40 mg/L SM treatment groups (P>0.05), while the MDR1
mRNA expression decreased in a concentration-dependent manner (P<0.05). Additionally, the HIF?1α and P?Gp protein
expression levels of the 10, 20, and 40 mg/L SM treatment groups decreased in a concentration-dependent manner compared
with the control group (P<0.05). Conclusion SM might reduce the expression of MDR1 by inhibiting the expression of HIF?1α
in HepG?2 cells at the post-transcriptional level, thereby reducing the drug resistance of hepatocellular carcinoma cells. |
| Department of Hepatobiliary Surgery, Central Hospital of Nanchong, Nanchong 637000, Sichuan, China;2.
Department of respiratory, Central
Hospital of Nanchong, Nanchong 637000, Sichuan, China |
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Abstract Objective To investigate the effect of silymarin (SM) on the expression of hypoxia-inducible factor-1 alpha
(HIF⁃1α) and multidrug resistance 1 (MDR1) in HepG⁃2 cells under hypoxia. Methods After treatment of HepG⁃2 cells with
different concentrations of SM (0, 10, 20, 40 mg/L) and concentration gradient chemotherapeutic drugs (doxorubicin, sorafenib,
cisplatin), MTT assay was used to detect the effect of different concentrations of SM on the sensitivity of HepG⁃2 cells to
chemotherapeutic drugs. Under hypoxic conditions, HepG⁃2 cells were treated with SM at 0, 10, 20, and 40 mg/L for 8 h, RTPCR was used to detect the effects of different concentrations of SM on the expression levels of HIF⁃1α and MDR1 mRNA, and
Western Blot was used to detect the effects of different concentrations of SM on the protein expression levels of HIF⁃1α and Pglycoprotein (P⁃Gp) in HepG⁃2 cells. Results With the increase of SM concentration, the sensitivity of HepG⁃2 cells to the
chemotherapy drugs doxorubicin, sorafenib and cisplatin gradually increased. Compared with the control group, there was no
significant difference in HIF⁃1α mRNA expression in the 10, 20, and 40 mg/L SM treatment groups (P>0.05), while the MDR1
mRNA expression decreased in a concentration-dependent manner (P<0.05). Additionally, the HIF⁃1α and P⁃Gp protein
expression levels of the 10, 20, and 40 mg/L SM treatment groups decreased in a concentration-dependent manner compared
with the control group (P<0.05). Conclusion SM might reduce the expression of MDR1 by inhibiting the expression of HIF⁃1α
in HepG⁃2 cells at the post-transcriptional level, thereby reducing the drug resistance of hepatocellular carcinoma cells.
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