For the in vivo study, they engrafted HNSCC in a mouse model and compared tumor growth in animals treated with radiation, esomeprazole, and combination of radiation with esomeprazole.
They found that esomeprazole inhibits tumor growth and dose-dependently enhances the cell killing effect of ionizing radiation in wildtype and p53-mutant radioresistant cancer cells.
Mechanistic studies demonstrate that esomeprazole arrests cancer cells in the G1 phase of the cell cycle through upregulation of p21 protein and inhibition of cyclin-dependent kinases type 1 and type 2.
This Oncotarget Research Output indicates that esomeprazole sensitizes cancer cells to ionizing radiation, and is associated with upregulation of p21 to arrest cells in the G1 phase of the cell cycle.
Dr. Yohannes T. Ghebre from The Baylor College of Medicine said, “Radiation therapy is a standard of care approach in the treatment of cancer patients who are medically inoperable or have surgically unresectable tumors.”
Luciani et al, for example, assessed the sensitivity of several treatment-resistant human cancer cell lines upon treatment with the PPIs esomeprazole and omeprazole, and their data shows that pretreatment of the cancer cells with the PPIs resulted in order of magnitude reduction in the half maximal inhibitory concentration values for the chemotherapeutic agents cisplatin, vinblastine and 5-fluorouracil compared to no PPI control.
Additionally, their in vivo study demonstrated that pretreatment of engrafted tumors with PPIs increased sensitivity of the tumor cells to cisplatin resulting in significant reduction in tumor weight.
Several other studies in mice, cats and dogs have demonstrated significant improvements in the sensitivity of tumor cells derived from kidney cancer, gastric cancer, esophageal cancer, adenocarcinoma, osteosarcoma and lymphomas to several anticancer drugs upon pretreatment with PPIs.
Some of the proposed mechanisms for the chemo sensitizing effect of PPIs include the effect of the drug on cancer cell invasion, migration and adhesion; buffering the acidic tumor microenvironment; as well as increased chemotherapeutic drug uptake by the tumor cells.
In line with the increased chemo sensitizing effect of PPIs in solid tumor-derived cancer cells in preclinical models, clinical studies also reported that PPIs are associated with beneficial outcomes in cancer patients including those with refractory disease.
Source: Eurekalert
