Polyphyllin VII is a Potential Drug Targeting CD44 Positive Colon Cancer Cells

Abstract

Background: Current therapies for colon cancer are hindered by treatment failure and recurrence, mainly due to colon cancer stem cells (CSCs). Thus, treatment using drugs targeting CSCs should be effective in eliminating colon cancer cells and impeding cancer recurrence. Objective: This study aimed to test if PPVII can be a potent drug candidate for the treatment of colon cancer by targeting CD44 positive colon cancer cells. Methods: In this study, we first demonstrated that CD44 is highly expressed in colon cancer tissues by TCGA/GTEX database analysis and immunohistochemical staining. Results: In this study, we first demonstrated that CD44 is highly expressed in colon cancer tissues by TCGA/GTEX database analysis. CD44 had high accuracy as a diagnostic and predictive index for colorectal cancer through receiver operating characteristic curve (ROC) analysis. At the same time, survival curve analysis also showed that the high expression of CD44 was associated with poor prognosis in patients with colon cancer. CD44’s higher expression in colon cancer tissues was further confirmed by immunohistochemical staining; the positive rate of CD44 expression was 87.95%. Then, one of the constituents that derives from the root of Paris polyphylla, Polyphyllin VII (PPVII), has been confirmed to inhibit the migration of colon cancer cells. Our results also demonstrated that PPVII could inhibit the sphere-forming ability of colon cancer cells. Further experiment results showed that PPVII could downregulate the expression of CD44 in colon cancer cells. In addition, PPVII was proved to have inhibitory effects against CD44 positive colon cancer cells. Conclusion: Therefore, PPVII might be a potent candidate reagent for the treatment of colon cancer by targeting CD44 positive colon cancer cells.