Fisetin enhances cisplatin sensitivity in renal cell carcinoma via the CDK6/PI3K/Akt/mTOR signaling pathway

Jiang,Tingting; Liang,Yan; Ji,Yenan; Xue,Yin

doi:10.3892/ol.2024.14298

Fisetin enhances cisplatin sensitivity in renal cell carcinoma via the CDK6/PI3K/Akt/mTOR signaling pathway

Authors:
- Tingting Jiang
- Yan Liang
- Yenan Ji
- Yin Xue
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Affiliations: Department of Traditional Chinese Medicine, Changzhou Wujin People's Hospital, Changzhou, Jiangsu 213100, P.R. China, Department of Emergency Center, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong 266042, P.R. China, Department of Colorectal Anal Surgery, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong 266042, P.R. China, Department of Traditional Chinese Medicine, Changzhou Wujin People's Hospital, Changzhou, Jiangsu 213100, P.R. China
Published online on: February 20, 2024 https://doi.org/10.3892/ol.2024.14298
Article Number: 165
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin resistance is ubiquitous among patients with renal cell carcinoma (RCC). The present study assessed the role of fisetin in regulating cisplatin sensitivity and increasing the efficacy of chemotherapy for patients with RCC. Cell Counting Kit‑8 and colony formation assays were used to assess the proliferation of RCC cells after fisetin and cisplatin treatment. The mRNA expression levels of cyclin‑dependent kinase (CDK)6 were evaluated using reverse transcription‑quantitative PCR. The expression levels of CDK6 and key proteins of the PI3K/Akt/mTOR signaling pathway were assessed using western blotting. The present study demonstrated that fisetin inhibited the proliferation and colony‑forming ability of RCC cells, and induced apoptosis and cell cycle arrest in a dose‑dependent manner. Additionally, fisetin enhanced the antineoplastic effects of cisplatin, as demonstrated by the increase in proliferation inhibition and apoptosis promotion after fisetin and cisplatin combination treatment. Furthermore, fisetin regulated the PI3K/Akt/mTOR signaling pathway through CDK6 inhibition, which enhanced cisplatin sensitivity. Overexpression of CDK6 neutralized the positive effects of fisetin on the improvement of cisplatin sensitivity in RCC cells. In conclusion, fisetin may enhance the sensitivity of RCC cells to cisplatin via the CDK6/PI3K/Akt/mTOR signaling pathway.

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