Colorectal cancer is one of the most common
cancers.
Regorafenib is used in patients with metastatic
colorectal cancer and sometimes, the
cancer cells become resistant to the drug. However, increased IGF-1R activity is associated with the invasion of
cancer cells. Therefore, it is thought that inhibiting IGF-1R by
Linsitinib and
Aspirin, the resistance of
colorectal cancer cells to
Regorafenib can be reduced. SW48
colon cancer cell line was cultured, resistance to the
regorafenib and exposed to
Linsitinib and
Aspirin. The treatment cytotoxicity, Flow cytometry for determine cancer stem cell markers, and the
mRNA expression of CD133, CD44, CD24, IGF1-R, CDX2 and PTEN were done. Then C57BL/6J mice
tumor model was produced and treated with
regorafenib,
aspirin, and
linsitinib. At least, Clinical symptoms, the levels of
IL-6, and IL-1β, TNF-α and MCP-1 in the colon tissues and sera were assessed. The
linsitinib and
aspirin as the IGF1-R antagonists inhibited
colon cancer resistance against
regorafenib, stem-cell like
colon cancer cells growth, decreased expression of CD133, CD44, CD24, and also increased CDX2, PTEN gene expression. In the canceroous mice,
linsitinib,
aspirin and
regorafenib treatment enhanced
Body weight and survival, and also decreased fecal blood, number of
tumors in colon and Inflammatory
cytokines levels in serum and colon tissues. In this study, we obtained the best in-vitro and in-vivo result of
colon cancer treatment when combinitation
therapy Linsitinib,
Aspirin, and
Regorafenib was used, and could prevent
tumor resistance, stem cell producing, pathological interaction and disease activity index.