Effect and Mechanism of Anlotinib on the Malignant Biological Behavior of Cisplatin-resistant Cells in Cervical Cancer

Purpose: To explore the effect of anlotinib on the proliferation, apoptosis, migration and invasion of cisplatin-resistant cervical cancer cells and study the changes of gene transcriptome of cisplatin-resistant cervical cancer cell lines after intervention with anlotinib. Materials and Methods In this study, cisplatin was used to induce the establishment of a drug-resistant cervical cancer cell line Siha/DDP. Then we use CCK-8 test, cell cloning test, flow cytometry test and western blotting test to explore the effect of anlotinib on the proliferation and apoptosis of Siha/DDP cells. Cell scratch test and transwell test were used to explore the effect of anlotinib on the migration and invasion of Siha/DDP cells. Finally transcriptome sequencing was used to detect changes in the gene expression profile of Siha/DDP cells under the action of anlotinib. Results Compared with the control group, the anlotinib group was able to dose-dependently inhibit Siha/DDP cell proliferation, migration, and invasion and significantly inhibit Siha/DDP cell clone formation; it was also able to dose-dependently promote Siha/DDP cell apoptosis and block Siha/DDP cells in the G2/M phase. Anlotinib significantly upregulated Bax, P21, E-cadherin protein expression and significantly downregulated Bcl-2, CDK1 and CyclinB1, VEGF, MMP-9 protein and drug resistance-associated protein P-gp protein expression in Siha/DDP cells. The gene expression profile of Siha/DDP cells caused changes after treatment with anlotinib. SQLE, MSMO1, LSS, FDFT1 and HMGCS1 were obtained as key hub gene Conclusion Anlotinib can inhibit the proliferation, migration and invasion of Siha/DDP cells and promote their apoptosis. The gene expression profile of Siha/DDP cells was altered after treatment with anlotinib, causing differential expression of several genes including SQLE, MSMO1, LSS, FDFT1 and HMGCS1.