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| Effects of 18β-glycyrrhetinic acid on autophagy and apoptosis of cervical cancer cells and transplanted tumor in nude mice by regulating PIM1 |
| Hits 218 Download times 131 Received:November 09, 2023 |
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| DOI
10.11656/j.issn.1672-1519.2024.04.20 |
| Key Words
18β-glycyrrhetinic acid;cervical cancer;PIM1;molecular docking |
| Author Name | Affiliation | E-mail | | WANG Yue | Postgraduate Training base of Suizhou Central Hospital Affiliated to Hubei University of Medicine, Jinzhou Medical University, Suizhou 441300, China
Suizhou Center for Disease Control and Prevention, Suizhou 441300, China | | | ZHANG Min | Postgraduate Training base of Suizhou Central Hospital Affiliated to Hubei University of Medicine, Jinzhou Medical University, Suizhou 441300, China | | | XIE Mingshui | Postgraduate Training base of Suizhou Central Hospital Affiliated to Hubei University of Medicine, Jinzhou Medical University, Suizhou 441300, China | 1365589033@qq.com |
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| Abstract
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| [Objective] To investigate the effects of 18β-glycyrrhetinic acid（18β-GA） on autophagy and apoptosis of cervical cancer cells and transplanted tumor in nude mice by regulating provirus integration site for moloney murine leukemia virus-1（PIM1）. [Methods] Hela cells were subjected to 18β-GA with concentration gradients（50 μmol/L，100 μmol/L，150 μmol/L），and the morphological changes of the cells were observed by bright field and immunofluorescence staining. The molecular docking of 18β-GA with PIM1 was performed using AutoDock Vina software. Hela cells with PIM1 knock down and overexpressing were treated with 100 μmol/L 18β-GA，the proliferation inhibition rate was detected by MTT method，and the protein expression of Hela cells was detected by western blot. Cervical cancer transplantation tumor model of nude mice was established with cervical cancer Hela cells，and after the tumor formation the mice were randomly divided into 18β-GA experimental group and control group，and 100 mg/kg 18β-GA and the same amount of normal saline solution were administered daily，respectively. After 14 days，the grafted tumor sections were taken，and the tissue morphology of the grafted tumor was compared by HE staining，and the protein expression level of the grafted tumor was compared by immunofluorescence staining and Western blot detection. [Results] Compared with the control group，with the increase of 18β-GA concentration，the expressions of PIM1 and B-cell lymphoma-2（BCL-2） were decreased，the expression of autophagy protein Beclin-1 was increased，and the cell proliferation inhibition rate was increased（P<0.05）. There were no significant differences in cell proliferation inhibition rate，expression levels of PIM1，Beclin-1 and BCL-2 after knocking down PIM1 followed by treating with 18β-GA（P>0.05），but there were significant differences between overexpression of PIM1 and overexpression of PIM1 were followed by addition of 18β-GA（P<0.05）. 18β-GA can be stably bound with PIM1 to PHE-100 with a binding energy of -7.3 kcal/mol. Transplanted tumor detection showed that 18β-GA inhibited the expression of PIM1 and interleukin-6（IL-6），decreased the phosphorylation of signal transducer and activator of transcription 3（STAT3），inhibited the expression of proliferation-related protein proliferating cell nuclear antigen（PCNA），anti-apoptotic protein BCL-2，and increased the expression of Beclin-1（P<0.05）. [Conclusion] By inhibiting PIM1 and then down-regulating BCL-2，18β-GA promotes Beclin-1 expression，promotes autophagy and apoptosis of cervical cancer cells，reduces STAT3 phosphorylation and decreases PCNA and IL-6 expression in transplanted tumor of nude mice，and thus plays a tumor suppressive effect on Hela cervical cancer mice. |
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