1. Academic Validation
  2. Flavokawain B Inhibits Growth of Cholangiocarcinoma Cells by Suppressing the Akt Pathway

Flavokawain B Inhibits Growth of Cholangiocarcinoma Cells by Suppressing the Akt Pathway

  • In Vivo. 2023 May-Jun;37(3):1077-1084. doi: 10.21873/invivo.13182.
Jun Hyuk Son 1 Young Hoon Choi 2 Sang Hyub Lee 3 Woo Hyun Paik 4 Ji Kon Ryu 4 Yong-Tae Kim 4
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea.
  • 2 Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • 3 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea gidoctor@snu.ac.kr.
  • 4 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Abstract

Background/aim: Cholangiocarcinoma is a devastating malignancy with limited treatment options and poor prognosis. Natural Products have gained considerable attention for showing antitumor effects with less toxicities. Flavokawain B (FKB), a natural product, has been studied for its antitumor effects on various Cancer cells. However, the anti-tumor effect of FKB on cholangiocarcinoma cells remains unknown. This study aimed at investigating the antitumor effect of FKB on cholangiocarcinoma cells in vitro and in vivo.

Materials and methods: SNU-478, a human cholangiocarcinoma cell line, was used in this study. Effects of FKB on cell growth inhibition and Apoptosis were investigated. The synergistic anti-tumor effect of FKB and cisplatin in combination was also evaluated. Western blotting was performed to examine the underlying molecular mechanisms of the effect of FKB. A xenograft mouse model study was performed to investigate the effect of FKB in vivo.

Results: FKB inhibited cell proliferation of cholangiocarcinoma cells in a concentration- and time-dependent manner. FKB also induced cellular Apoptosis additively in combination with cisplatin. Akt pathway was suppressed by FKB either alone or in combination with cisplatin. In the xenograft model, FKB treatment in combination with cisplatin/gemcitabine significantly inhibited tumor growth of SNU-478 cells.

Conclusion: FKB showed an antitumor effect through the induction of Apoptosis, which was mediated by suppressing the Akt pathway in cholangiocarcinoma cells. However, the synergistic effect of FKB and cisplatin was not definite.

Keywords

Akt; Cholangiocarcinoma; P-Akt; cisplatin; flavokawain; gemcitabine.

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