The Epithelial-mesenchymal Transition And Drug Resistance In Ovarian Cancer Cell

Chemoresistance remains the major therapeutic barrier in clinical cancer therapy.Epithelial ovarian cancer is the major cause of death among women with gynecologicalmalignancies. Paclitaxel is commonly used for chemotherapy of ovarian cancer, yet itsefficacy is limited by chemoresistance. Generally, drug resistance is associated with diversemechanisms in cancer. The aim of the present study was to determine whether the EMT isinvolved in acquired resistance to paclitaxel in A2780human ovarian cancer cells and whetherthere is a link between EMT and CSC enrichment.Our study used wild-type (A2780/WT) and paclitaxel-resistant human epithelial ovariancancer cells (A2780/PTX) to investigate the molecular mechanism of paclitaxel resistance andassociated cellular behaviors. Here we demonstrated that A2780/PTX cells underwent EMTprocesses. This was confirmed as follows:(i) morphological change from cobblestone-like tospindle-shaped cells,(ii) increased potential for proliferation and migration, and (iii) changes inmolecular markers (significant reduction in E-cadherin and laminin-5expression andup-regulation of N-cadherin, vimentin and fibronectin). Moreover, several studies havedemonstrated that the EMT plays an important role in functional malignancy behaviors likefacilitating the transformation, initiation, progression, and metastasis of human cancers. Wefurther examined the proliferation in these two cell types. As expected, our findings showedthat A2780/PTX cells displayed enhanced multiplication in the MTT assay. Overall, weobtained evidence that paclitaxel resistance and facilitated malignant potential are linked withthe EMT. Since the PI3K/Akt axis is frequently activated in human cancer, we focused on theEMT with particular emphasis on the PI3K/Akt pathways involved in the regulation ofmalignancy. To determine whether the PI3K pathway was involved in the process, the PI3Kinhibitor LY294002was applied to A2780/PTX cells, resulting in inhibition of fibroblasticmorphology, proliferation and motility. Our evidence seems to be associated with otherresearch in Gefitinib-resistant cells from a head and neck squamous cell carcinoma cell line.Furthermore, we found that the inhibition of PI3K activity attenuated the paclitaxel resistanceand led to loss of cell polarity in terms of β-tubulin distribution suggested that there should alsobe defects in cell migration and invasion. Moreover, LY294002, when added to A2780/PTXcells, abolished colony formation. Although further studies are needed to elucidate thechemoresistance mechanisms in PI3K-mediated drug-resistance, the use of PI3K inhibitorsduring chemotherapy could be a useful approach to improve its efficacy.we used wild-type (A2780/WT) and paclitaxel-resistant human epithelial ovarian cancercells (A2780/PTX) to investigate the expression of ALDH1and the associated capacity forcolony formation with soft agar clone formation assay. We found that A2780/PTX cellsdisplayed high ALDH1activity. Next, we examined colony-formation by A2780/PTX cells.As anticipated, our findings showed that A2780/PTX cells displayed enhancedcolony-formation in the soft agar assay. This indicated that A2780/PTX cells were moretumorigenic than wild-type A2780/WT cells.We are the first to report that PI3K inhibition reversed paclitaxel resistance-induced EMT,increased the sensitivity to paclitaxel and reduce the tumorgenic in A2780human ovarian cancer cells, indicating that the PI3K pathway is a promising therapeutic target againstovarian cancer with paclitaxel chemotherapy, but it still need to find the mechanism of PI3Kinvolved in EMT and drug-resistance.