HMQ‑T‑F2 suppresses migration of the human cervical cancer HeLa cells by reversing EMT via the PI3K/Akt signaling pathway

Abstract

Epithelial-mesenchymal transition (EMT) is closely related to tumor metastasis, and offers insight into novel strategies for cancer treatment. HMQ-T-F2 (F2) is a taspine derivative, which has excellent anticancer activity in human cervical cancer. The present study aimed to evaluate the effect of F2 on in vitro migration of HeLa cells. The present data demonstrated that F2 inhibited migration of HeLa cells by negatively regulating the Wnt signaling pathway and reversing EMT. F2 not only mediated Frizzled8, p-LRP6 and LRP6 expression, but also downregulated the phosphorylation of GSK3β, and concurrently decreased the nucleus protein expression of MMP2, MMP3, MMP7, MMP9, and c-Myc. In addition, the expression of N-cadherin, vimentin, Snail and HIF-1α were downregulated and that of E-cadherin was upregulated after F2 treatment. F2 was also associated with the downregulation of the PI3K/Akt/mTOR signaling pathways. Notably, F2 induced HeLa cell accumulation at the S phase and cell apoptosis. These results provide evidence that F2 inhibits HeLa cell migration, proliferation and promotes apoptosis. It also reverses EMT, potentially via the PI3K/Akt signaling pathway. Therefore, F2 may be a potential therapeutic reagent against cervical cancer.

Effect of Anti-Programmed Cell Death Protein-1 Antibody Combined with Paclitaxel on Cervical Cancer via Phosphoinositide 3-Kinase/Protein Kinase B Pathway in Rats

“…PD-1 antibodies and PD-L1 ligand can stimulate T cell activity, so that a large number of cells are blocked in resting phase/growth 1 phase (G0/G1) phase, inhibit cell growth and promote their apoptosis. In addition, anti-PD-1 antibody combined with paclitaxel can inhibit extracellular regulated kinase (ERK) and PI3K-Akt signaling pathway and further inhibit the expression of proteins and genes related to the mitotic process, thereby affecting cell cycle, further inhibiting the proliferation of cervical cancer cells and promoting cell apoptosis [8][9][10][11][12][13][14][15][16][17] . In the study of Li et al [18] , the effect of paclitaxel chemotherapy on nude mice with cervical cancer transplantation tumors was assessed.…”

LncRNA HOTAIR Promotes Chemoresistance by Facilitating Epithelial to Mesenchymal Transition through miR-29b/PTEN/PI3K Signaling in Cervical Cancer

“…Consequently, transfection of miR-29b mimics resulted in significant upregulation of PTEN and downregulation of PI3K in cervical cancer cells. PTEN acts through the PI3K-mediating signaling pathway, which is closely correlated with EMT that fuels therapeutic resistance and the growth and migration of cervical cancer cells [Che et al, 2019;Dai et al, 2019]. Hence, changes in protein ex-pression associated with EMT and the alterations in HOTAIR and miR-29b were explored in the present study.…”

DYNLT3 overexpression induces apoptosis and inhibits cell growth and migration via inhibition of the Wnt pathway and EMT in cervical cancer

“…Dvl3, as a multivalent scaffold with several well-known domains, is significantly upregulated in cervical cancer and participates in cervical cancer oncogenesis via Wnt/b-catenin activation (34). LRP6, a Wnt coreceptor, shows increased expression in cervical cancer and may serve as an oncoprotein by blocking Wnt/b-catenin signaling (35). C-Myc acts as an oncogene to control multiple biological processes, and its high expression could promote the proliferation and metastasis of cervical cancer, which may play a synergistic role in the pathogenesis of cervical cancer (36,37).…”