Aspirin Inhibiting The Development Of Esophageal Squamous Cell Carcinoma And Enhancing Its Responsiveness To Cisplatin

The incidence of malignant tumor is ever-increasing around the world and has been a great burden to the health care system in China. Esophageal carcinoma (EC) is one of the most lethal malignancies, the incidence of which ranks eighth among all cancers. Over 70% of EC cases occur in China,90% of them being esophageal squamous cell carcinoma (ESCC). Therefore, the investigation of ESCC is of special importance to the health care of Chinese residents.The prognosis of EC is relatively poor. Due to lack of methods of early diagnosis, a majority of patients come to see a doctor at a late stage. As a result, the excision rate is low, and in many cases, surgery is unsuitable for the patient. Chemotherapy is usually less effective in ESCC, with no significant improvement all these years. In total, the 5-year survival rate of EC is merely 23%.The use of aspirin in prevention of colorectal carcinoma has become unanimously agreed. The adjuvant effect of aspirin in treatment of cancer has also come into spotlight. A series of clinical studies has shown a positive role of aspirin in prolongation of survival in patients with colon cancer by reducing the metastasis and recurrence. A few studies also suggest aspirin lowering the risk of EC. However, there is no clear evidence by now that aspirin could prevent EC or improve the treatment of EC patients. The mechanism of its adjuvant effect in cancer treatment is yet to be explored.In this study, we proved that aspirin could prevent the growth of esophageal tumor using an NMBA-induced ESCC model. It also showed an inhibitory effect on the sternness of ESCC cells. We demonstrated an improvement in the effect of cisplatin when combining aspirin in treating transplanted tumors in nude-mice. Aspirin significantly enhanced the cytotoxic effect of cisplatin. The resistance of esophageal cancer cell to cisplatin was lowered through a series of mechanisms with the treatment of aspirin. By inhibiting the phosphorylation of ATM, the repairing of DNA damage was down-regulated. There was also a decrease in the efflux activity and ALDH1 activity of the tumor cells. Blockades of PI3K/Akt pathway was detected.In sum, our results demonstrated a positive role of aspirin in the prevention and treatment of EC. Our study revealed a possible application of aspirin in treatment of cancer.