Kaempferol inhibits the growth and metastasis of cholangiocarcinoma <italic>in vitro</italic> and <italic>in vivo</italic>

Abstract

Kaempferol is a flavonoid that has been reported to exhibit antitumor activity in various malignant tumors. However, the role of kaempferol on cholangiocarcinoma (CCA) is largely unknown. In this article, we found that kaempferol inhibited proliferation, reduced colony formation ability, and induced apoptosis in HCCC9810 and QBC939 cells in vitro. Results from transwell assay and woundhealing assay demonstrated that kaempferol significantly suppressed the migration and invasion abilities of HCCC9810 and QBC939 cells in vitro. Kaempferol was found to decrease the expression of Bcl-2 and increase the expressions of Bax, Fas, cleaved-caspase 3, cleaved-caspase 8, cleaved-caspase 9, and cleaved-PARP. In addition, kaempferol also downregulated the levels of phosphorylated AKT, TIMP2, and MMP2. In vivo, it was found that the volume of subcutaneous xenograft (0.15 cm 3 )in the kaempferol-treated group was smaller than that (0.6 cm 3 ) in the control group. Kaempferol also suppressed the number and volume of metastasis foci in the lung metastasis model, with no marked effects on body weight of mice. Immunohistochemistry assay showed that the number of Ki-67-positive cells was lower in the kaempferol-treated group than that in the control group. We further confirmed that the changes of apoptosis-and invasion-related proteins after kaempferol treatment in vivo were similar to the results in vitro. These data suggest that kaempferol may be a promising candidate agent for the treatment of CCA.

Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1

“…The consumption of kaempferol has been reported to significantly increase the cytotoxic effects of cisplatin 29. In in vivo xenografted mouse models, kaempferol inhibits the growth and metastasis of cholangio-carcinoma in vivo 30. The volume of subcutaneous xenograft in the kaempferol-treated group was smaller than that in the cholangiocarcinoma control group 30.…”

“…In in vivo xenografted mouse models, kaempferol inhibits the growth and metastasis of cholangio-carcinoma in vivo 30. The volume of subcutaneous xenograft in the kaempferol-treated group was smaller than that in the cholangiocarcinoma control group 30. Kaempferol also suppressed the number and volume of metastasis foci in the lung metastasis model 30.…”

“…The volume of subcutaneous xenograft in the kaempferol-treated group was smaller than that in the cholangiocarcinoma control group 30. Kaempferol also suppressed the number and volume of metastasis foci in the lung metastasis model 30. Song et al also found that kaempferol, administered 20 mg/kg/day intraperitoneal injection (i.p.)…”

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

“…In HCCC9810 and QBC939 cells, kaempferol suppressed proliferation, reduced colony formation, and induced apoptosis. Additionally, it (a) decreased Bcl‐2 expression, (b) increased Fas, Bax expressions, (c) enhanced cleaved‐caspase 3, cleaved‐caspase 8, cleaved‐caspase 9, and cleaved‐PARP, (d) down‐regulated levels of phosphorylated TIMP2, AKT, and MMP2, and (e) inhibited the number and volume of metastasis foci in lung metastasis model (Qin, Cui, Yang, & Tong, ).…”

Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

“…Another study examined the inhibitory effect of kaempferol on cholagiocarcinoma. The in vitro and in vivo studies demonstrated that kaempferol decreases the level of Bcl‐2 and also enhances the level of Bax, Fas, cleaved Caspases 3, 8, and 9 as well as cleaved‐PARP, leading to the inhibition of growth and metastasis of cholangiocarcinoma (Qin et al, ).…”