Compound Kushen Injection Promoted the Killing Effect of Cytokine-Induced Killer Cells Which Was Activated by Dendritic-Colon Cancer Stem Cell Fusion Cells on Colon Cancer Stem Cells

Abstract

Colon cancer stem cells (cCSCs) are highly tumorigenic and resistant to traditional chemotherapeutic drugs. Therefore, they are an essential factor in colorectal cancer (CRC) metastasis and recurrence. Dendritic cells (DCs) could bind to the tumor cells and form the fusion cells (FCs). And these FCs could inhibit the development of malignant tumors. Furthermore, the cytokine induced killer (CIK) cells (CD3+ /CD56+ T lymphocytes) could also apply for the immunotherapy of cancer. And compound Kushen injection (CKI) is a traditional Chinese medicine (TCM) which has been used for the treatment of various tumors. However, whether the dendritic-colon cancer stem cell fusion cells (DC-cCSC FCs) could activate the CIK cells and kill the colon cancer stem cells is unknown. And whether the CKI could enhance the lethal effect is still unclear. In this study, we collected peripheral blood samples from healthy participants to acquire mononuclear cells and induced DC and CIK cells. Meanwhile, the CD44+ cells (cCSCs) were screened from SW480 cells. Next, the DC-cCSC FCs were established for the next experiments. At last, CCK-8 assays were performed to determine the effect of DC-cCSC FCs and CKI on the viability of cCSCs. We found that DC-cCSC FCs enhanced the proliferation of CIK cells and induce the CIK cells to secrete more IL-12. The DC-cCSC FCs enhanced the inhibitory effect of CIK cells on cCSCs. Furthermore, application of CKI enhanced the killing rates of DC-cCSC FCs and CIK cells on cCSCs. CIK cells activated by the DC-cCSC FCs had the lethal effect on the cCSCs. Furthermore, CKI enhanced this lethal effect of DC-cCSC FCs and CIK cells.