RESUMEN
Store-operated calcium entry (SOCE) is an important pathway for calcium signaling that regulates calcium influx across the plasma membrane upon the depletion of calcium stores in the endoplasmic reticulum. SOCE participates in regulating a number of physiological processes including cell proliferation and migration while SOCE dysregulation has been linked with pathophysiological conditions such as inflammation and cancer. The crosslink between cancer and inflammation has been well-established where abundant evidence demonstrate that inflammation plays a role in cancer pathophysiology and the response of cancer cells to chemotherapeutic agents including cisplatin. Indeed, the efficacy of cisplatin against cancer cells is reduced by inflammation. Interestingly, it was shown that SOCE enhances inflammatory signaling in immune cells. Therefore, the main objectives of this study are to examine the impact of SOCE inhibition on the cisplatin sensitivity of breast cancer cells and to explore its related mechanism in modulating the inflammatory response in breast cancer cells. Our findings showed that SOCE inhibitor (BTP2) enhanced cisplatin cytotoxicity against resistant breast cancer cells via inhibition of cell proliferation and migration as well as induction of apoptosis. We also found an upregulation in the gene expression of two major components of SOCE, STIM1 and ORAI1, in cisplatin-resistant breast cancer cells compared to cisplatin-sensitive breast cancer cells. In addition, cisplatin treatment increased the gene expression of STIM1 and ORAI1 in cisplatin-resistant breast cancer cells. Finally, this study also demonstrated that cisplatin therapy caused an increase in the gene expression of inflammatory mediators COX2, IL-8, and TNF-α as well as COX2 protein and upon SOCE inhibition using BTP2, the effect of cisplatin on the inflammatory mediators was reversed. Altogether, this study has proven the pivotal role of SOCE in cisplatin resistance of breast cancer cells and showed the importance of targeting this pathway in improving breast cancer therapy.
RESUMEN
Objective: The impact of pharmaceutical services on public health especially in regards to smoking cessation counseling can influence the rate of smoking cessation. The present study aims to evaluate prevalence, beliefs, and attitude of pharmacy students toward smoking habit and SC methods. Methods: An online cross-sectional survey was conducted among pharmacy students at King Saud University, Riyadh, Saudi Arabia over 4-month period from May to August 2021. The survey consisted of 22-items focused on evaluating the prevalence, belief, and attitude toward smoking habits and smoking cessation methods. Data was descriptively analyzed using a statistical package for social science version 26 (SPSS). Results: A total of 675 students completed the survey, among which 78.7 % were non-smokers and only 31.7% received education on the dangers of smoking. The most common methods of smoking cessation they heard of were consultation (58.6%), followed by use of electronic cigarettes (41.92 %) and Nicotine patch (40.7%). One-third of the surveyed students (36.8 %) agreed that specialized smoking cessation clinics enhance the efficacy of smoking cessation methods. The majority of students (80.6%) agreed to ban smoking in public places and 92.2% believed that tobacco sales to adolescents should be forbidden. Health professionals should actively participate and advise their patients to quit smoking as 89.8 % students agreed on that. Age and gender of students had significantly influenced the prevalence of smoking, history of smoking, frequency of smoking, efforts to quit smoking among smokers (p = 0.0001). Conclusion: The prevalence of non-smokers among pharmacy students is encouraging, yet level of awareness about and usefulness of smoking cessation methods is unsatisfactory. Therefore, the study clearly highlights a great need for integrating smoking cessation programs in their academic curricula to prepare them for real-world practice.