1. 青藤碱对 2 型糖尿病合并肝癌小鼠的治疗作用研究.
- Author
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闫丽晶, 孙焕焕, 陈羽玲, 于晓慧, 张静茹, and 李培杰
- Subjects
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LIVER proteins , *LIVER cells , *CANCER cell growth , *P53 protein , *GLUTATHIONE peroxidase , *KI-67 antigen - Abstract
Objective: To investigate the therapeutic effect and possible mechanism of sinomenine(SIN) on type 2 diabetic(T2DM) mice with liver cancer(HCC). Methods: Eight-week-old male BALB/c mice(20-25 g) were divided into Control, T2DM+HCC,SIN-L, SIN-M and SIN-H group. Mice in the Control group were fed normally, and mice in other groups were injected intraperitoneally with streptozotocin(STZ) and inoculated with hepatocellular carcinoma cells(H22) in liver parenchyma to establish T2DM combined with HCC mice model. Mice in the SIN-L, SIN-M and SIN-H group were intraperitoneally injected with 10, 20 and 40 mg/kg/d of sinomenine, respectively. Mice in the Control group and T2DM+HCC group were intraperitoneally injected with 0.5 m L of normal saline respectively. All the mice were treated for 21 days. 24 hours after the last administration, the liver index was calculated and fasting blood glucose(FPG), fasting insulin(FINS), serum total cholesterol(TC), triglyceride(TG)], alanine aminotransferase(ALT), aspartate aminotransferase(AST) and lactate dehydrogenase(LDH), liver superoxide dismutase(SOD), catalase(CAT), Glutathione peroxidase(GSH-PX)and malondialdehyde(MDA) levels were detected. Liver morphology was observed by hematoxylin and eosin(HE) staining. The protein expression of BCL2, BAX, P53, signal transducer and activator of transcription 3(STAT3), cytokine signal inhibitor 3(SOCS3) and sterol regulatory element binding protein-1(SREBP-1) in liver tissue were detected by Western blot. Results: The median survival time of T2DM+HCC group, SIN-L group, SIN-M group and SIN-H group was 25, 32, 35 and 41 days respectively(P<0.001), the median survival time of mice extended with the increase of sinomenine concentration. Compared with T2DM+HCC group, the levels of FPG, FINS, TC and TG in SIN-L, SIN-M and SIN-H group decreased, serum ALT, AST and LDH levels decreased, the basic rules of hepatic cell arrangement, edema, vacuolar degeneration, inflammatory cell infiltration and other lesions were significantly reduced, liver index decreased, liver SOD, CAT and GSH-PX levels increased, liver MDA level decreased, liver BCL2 protein expression decreased, liver BAX and P53 protein expression increased(P<0.05). Compared with T2DM+HCC group, the expression of p-STAT3(Tyr705), SOCS3 and SREBP-1 protein in liver of SIN-L, SIN-M and SIN-H group decreased in a dose-dependent manner(P<0.05). Conclusion: Sinomenine can effectively prolong the survival time of type 2 diabetic mice with liver cancer, improve the blood glucose and lipid levels as well as the live function, and inhibit the growth of cancer cells, which may be related to the inhibition of STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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