Lathyrol inhibits the proliferation of renca cells by affecting the expression of TGF-β/smad pathway and then affecting the cell cycle

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Abstract

Background Renal cell carcinoma (RCC) is a prevalent malignant tumor with high morbidity and mortality. The TGF-β/smad signaling pathway plays a significant role in the development and progression of RCC. Methods This study explored the impact of lathyrol on the proliferation of mice RCC renca cells by inhibiting the TGF-β/smad signaling pathway and arresting the cell cycle. Bioinformatics analysis, cell culture experiments, and animal experiments were conducted to detect the effects of lathyrol on the activity, mRNA, and protein expressions of RCC cells and RCC xenograft tumors, as well as the expressions of cell cycle proteins and cell cycle regulatory proteins. Results Lathyrol treatment showed a positive correlation with the inhibitory effect on cell proliferation. The IC values of 786-O cells and renca cells were comparable. In vitro, lathyrol decreased the protein and mRNA expressions of TGF-β1, TGF-βR1, smad2, smad3, smad4, and smad9, while increasing the mRNA expressions of smad2, smad3, and smad4. In vivo, lathyrol suppressed the mRNA and protein expressions of TGF-β1, TGF-βR1, smad2, smad3, smad4, and smad9 in RCC xenografts, and decreased the protein expressions of cyclinD1, cyclinB1, cyclinA1, cyclinE1, CDK6, CDK4, and CDK1, while increasing the expressions of P16, P21, and P27. Conclusion Lathyrol can repress the expression of key proteins in the TGF-β/smad signaling pathway, impede the signal transduction, arrest the cell cycle progression of renca cells, and subsequently inhibit the proliferation of RCC cells. Future studies are needed to further explore the mechanism of lathyrol in RCC treatment.

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