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Digestive Diseases and Sciences

Digestive Diseases and Sciences

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Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis

Published:1 February 2024 DOI: 10.1007/s10620-023-08210-x PMID: 38170336
Haishan Deng,?Xiaomei Qian,?Yongtao Zhang,?Wenlong Yu,?Ping Yang

Abstract

Background: Cholangiocarcinoma (CCA) is a malignant tumor with a high mortality rate. Resistance to chemotherapy remains a major challenge related to cancer treatment, and increasing the sensitivity of cancer cells to therapeutic drugs is a major focus of cancer treatment.

Aims: We purposed to explore the role of Metformin in CCA involved in chemotherapeutic sensitivity and Pyruvate kinase M2 (PKM2) through regulating mitochondrial apoptosis in the present study.

Methods: CCA cell lines of HCC9810 and RBE were treated with Metformin companied with antagonists or agonists of PKM2, cells sensitivity to Gemcitabine, cell migration and invasion along with apoptosis, which is mediated by JC-1 and LDH were assayed.

Results: Our results indicated that Metformin and Gemcitabine exhibit synergistic effect on inhibition of cholangiocarcinoma cell viability, cell migration and invasion as well as promotion apoptosis of cholangiocarcinoma cells. In vivo, Metformin combined with Gemcitabine has cooperation in inhibiting the growth of cholangiocarcinoma cell-derived tumors. Moreover, Metformin and Gemcitabine inhibited expression of PKM2 and PDHB in HCC9810 and RBE.

Conclusion: Our study suggested that Metformin may increase the response of cholangiocarcinoma cells to Gemcitabine by suppressing PKM2 to activate mitochondrial apoptosis.

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6-[(3-aMinophenyl)Methyl]-4,6-dihydro-4-Methyl-2-(Methylsulfinyl)-5H-Thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one 1221186-53-3 C17H16N4O2S2 152 suppliers $29.00-$3200.00
6-[(3-aMinophenyl)Methyl]-4,6-dihydro-4-Methyl-2-(Methylsulfinyl)-5H-Thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one 1221186-53-3 C17H16N4O2S2 152 suppliers $29.00-$3200.00
6-[(3-aMinophenyl)Methyl]-4,6-dihydro-4-Methyl-2-(Methylsulfinyl)-5H-Thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one 1221186-53-3 C17H16N4O2S2 152 suppliers $29.00-$3200.00
6-[(3-aMinophenyl)Methyl]-4,6-dihydro-4-Methyl-2-(Methylsulfinyl)-5H-Thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one 1221186-53-3 C17H16N4O2S2 152 suppliers $29.00-$3200.00
PKM2 inhibitor 94164-88-2 C18H19NO2S2 77 suppliers Inquiry
PKM2 inhibitor 94164-88-2 C18H19NO2S2 77 suppliers Inquiry
PKM2 inhibitor 94164-88-2 C18H19NO2S2 77 suppliers Inquiry
PKM2 inhibitor 94164-88-2 C18H19NO2S2 77 suppliers Inquiry

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