Conference Proceeding

Modulation of MUC-1 by vitamin D in pancreatic cancer

Dr. Sangeeta Choudhury,
Senior Consultant, Sir Ganga Ram Hospital, India

Dr. Sangeeta Choudhury carried her PhD at Bhabha Atomic Energy Research Centre, (BARC) Mumbai at the Department of Carcinogenesis & Tata Institute of Fundamental Research (TIFR), Mumbai. Presently she is working as a Senior Consultant, Department of Research, Sir Ganga Ram Hospital, India.

Over the years, pancreatic cancer has been established as a complicated disease with poor prognosis and survival rate. Standard chemotherapeutic agents/drugs have not shown any significant advancement in its regression. Several studies have indicated anti-angiogenesis and blocking the cancerous growth of breast, prostate, lung and colon by micronutrients like vitamin D, E, B12. Although, pancreatic cancer tissue expresses Vitamin D (VitD) receptor, the potential mechanism to exert anti-cancer effect remains underexplored. Thus, our study aimed to find out the mechanistic effect caused by the VitD analogue (Calcitirol) in pancreatic cancer cells. Pancreatic cancer cells (PCC lines; MiaPaCa2 and PanC-1) treated with calcitirol for longer duration (24hrs-to-96hrs) showed decreased expression of metastatic phenotype, CXCR4/CCL12, EpCAM/Vimentin along with decreased chemoresistant-MUC-1 expression, although no inhibitory effect was observed on their proliferative capacity. But, addition of Gemcitabine (Gem) to calcitirol-treated PCC lines increased their apoptotic capability than cells treated only with Gem, suggesting that calcitirol treated-PCC cells are susceptible to chemotherapeutic drug. Further, with the emergence of stroma playing a major role in pancreatic cancer, we attempted to elicit the involvement of VitD in Sonic Hedgehog (SHH) signaling. Enhanced apoptosis was observed when salinomycin (SHH inhibitor) was administered to calcitirol treated-PCC cells. Copy numbers of transcription factors C-myc, SMO, PTCH1, PTCH2, and hypoxia-induced factor (HIF1-α) were observed to show increased expression in treated PCC lines in comparison to untreated cells. In conclusion, our experimental evidence postulates a potential role of VitD-analogue, calcitirol modulating the pancreatic tumor-associated MUC-1 within its stromal niche.

Published: 11 May 2017