Finally, we demonstrated that OV alone or in combination with CDDP profoundly inhibited tumor growth while concurrently suppressing the tumorsphere-forming ability and decreasing EV cargos of miR-21-5p, mTOR, PI3K, STAT3, and β-catenin, indicating that OV enhances the sensitivity of CAL27 CSCs to CDDP and suppresses their tumor-initiating ability in vivo. The gene discussed is PIK3CA; the disease is neoplasm.