Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 8, August, p. 911–919

doi: 10.17219/acem/121919

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Dihydroartemisinin/miR-29b combination therapy increases the pro-apoptotic effect of dihydroartemisinin on cholangiocarcinoma cell lines by regulating Mcl-1 expression

Hui Hu1,A,D, Zongding Wang2,B, Chunlu Tan3,C,E, Xubao Liu3,A,D, Hao Zhang3,A,E, Kezhou Li3,A,F

1 Department of Traumatology, Central Hospital of Chongqing University, Chongqing Emergency Medical Center, China

2 Department of General Surgery, Peoples’s Hospital of Fengjie, Chongqing, China

3 Departments of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China

Abstract

Background. Cholangiocarcinoma is a malignant tumor that originates from the neoplastic transformation of bile duct epithelial cells.
Objectives. To investigate the role of DHA and miR-29b on the proliferation and apoptosis of cholangiocarcinoma cells, and to explore whether DHA exerted its role through the miR-29b/Mcl-1 signaling pathway.
Material and Methods. Human cholangiocarcinoma cell lines HUCCT-1 and FRH0201 were treated with dihydroartemisinin (DHA) and DHA+miR-29b. The inhibitory effects of DHA and miR-29b on proliferation were detected using MTT assay. The effects of DHA and miR-29b on apoptosis were detected using flow cytometry (FCM). The mRNA and protein expressions of Mcl-1L and Mcl-1S were evaluated with reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting, respectively.
Results. The DHA increased miR-29b expression in HUCCT-1 and FRH201 cells. The MTT assay showed that DHA+miR-29b combination therapy promoted the inhibition effects on the proliferation of HUCCT-1 and FRH201 cells. The FCM results revealed that DHA and miR-29b combination therapy increased the apoptosis of HUCCT-1 and FRH201 cells. The RT-PCR and western blotting analysis found that DHA+miR-29b combination therapy significantly decreased Mcl-1L expression and increased Mcl-1S expression in both HUCCT-1 and FRH201 cells. The Mcl-1S:Mcl-1L ratio was notably higher in the DHA+miR-29b combination therapy group than in the control group and DHA therapy group, in both HUCCT-1 and FRH201 cells.
Conclusion. The DHA and miR-29b have a pro-apoptotic effect on cholangiocarcinoma cells through the DHA/miR-29b/Mcl-1 pathway, possibly by upregulating the expression of the pro-apoptotic protein Mcl-1S and thus increasing the proportion of Mcl-1S protein among the total amount of Mcl-1 protein.

Key words

cholangiocarcinoma, miR-29b, dihydroartemisinin, Mcl-1

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