Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer

小檗碱通过抑制卵巢癌中的花生四烯酸代谢途径和 FAK 磷酸化来抑制化疗引起的细胞再增殖

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作者:Yawei Zhao, Lianzhi Cui, Yue Pan, Dan Shao, Xiao Zheng, Fan Zhang, Hansi Zhang, Kan He, Li Chen

Conclusions

Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.

Methods

The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot.

Results

Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA2 -AA-COX-2-PGE2 pathway by inhibiting the expression of iPLA2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Conclusions: Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.

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