Title : Impact of diclofenac on expression of POTE family genes POTEE and POTEB in epithelial ovarian cancer cell lines
Abstract:
Ovarian Cancer (OC) is the 3rd most common gynecological cancer worldwide with high morbidity and mortality rate and Epithelial Ovarian Cancer (EOC) is the most common subtype (90%). Despite advances in treatment, late diagnosis and inadequate therapeutic options continue to be the major challenges. Studies have shown that Non-Steroidal Anti Inflammatory Drugs (NSAIDS) like diclofenac and sulindac induce apoptosis in OC cells, inhibit tumorigenesis and metastasis. Their potential as effective chemotherapeutic agents is being studied.
POTE (prostate, ovary, testis and placenta expressed) family is a recently discovered primate specific multigene family whose expression is restricted to certain tissues and but highly expressed in certain cancers including OC. Though the exact functions of POTE genes is unknown yet, higher expression of POTE genes in germ cells of testis is found to be associated with apoptosis during spermatogenesis. We thus hypothesized that NSAIDs induced apoptosis can be linked to varied expression of POTE genes OC.
Our study investigates variation in expression of two POTE genes POTE E and POTE B against diclofenac, a potent NSAID in EOC cell lines, A2780 for POTEE and OVCAR4 for POTEB due to their higher expression in the respective EOC cell lines. The cell lines were treated with diclofenac of different concentrations and changes in gene expression were analyzed using qRTPCR and western blot techniques. Cell cycle and apoptosis assays were performed to assess the effects. Results showed that diclofenac treatment significantly induces apoptosis (p<0.001). There is a marked upregulation of POTEB in OVCAR4 (p<0.001) but a decrease in expression of POTEE gene in A2780 (p<0.001) compared to respective untreated controls.
The results suggest that diclofenac induced apoptosis of EOC cells can be mediated through the modulation of POTE genes expression especially POTEB gene. This further implies underlying biochemical processes that regulate tumorigenesis and cancer progression through altered expression POTE genes. But most importantly this paves way for further research on immunotherapy of OC where the POTE proteins are targeted and also the potential of NSAIDs as not only chemotherapeutic agents for OC but also to enhance the efficacy of immunotherapy for OC.
Key words: Ovarian Cancer, NSAIDs, diclofenac, POTE family genes, apoptosis
