Effect of insulin on the proliferation of colon cancer cells and the underlying mechanism, and the intervention effect of the ginsenoside compound K

• Main Authors: Pei-Yi Chu, 朱珮儀
• Other Authors: Gow-Chin Yen
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/11382306492548785743

碩士 === 國立中興大學 === 食品暨應用生物科技學系所 === 102 === The progression of multiple cancers, including liver, pancreatic, breast, colon/rectum and bladder cancer may exhibit a direct correlation between combination of hyperglycemia and hyperinsulinemia in diabetes mellitus (DM) patients. The survival rate of the patients with DM and colorectal cancer (CRC) is much lower than that of patients with CRC only, and hyperglycemia may be a mediator to induce hyperinsulinemia and increase cancer risk. Compound K (CK) is a metabolite of panaxndiol ginsenosides in the intestinal and possesses anti-cancer properties such as anti-proliferation, cell cycle arrest and pro-apoptotic effect on CRC cancer. CK has been considered to exhibit anti-cancer and improving diabetes. Therefore, the human colon cancer HCT 116 cell line was used to investigate the effect of insulin on cell proliferation and its underlying molecular mechanism, as well as the effect of CK on insulin-induced cell proliferation and metastasis. The results showed that insulin can promote the cell proliferation, migration and anchorage-independent growth of HCT116 cells. Insulin enhanced the expression of mRNA and activity of matrix metalloproteinases-2 (MMP-2) and MMP-9, leading to a rise of the metastatic ability in HCT 116 cells. The results also showed that insulin combined with its insulin receptor (IR) to activate insulin receptor substrate 1 (IRS-1), which altered its downstream signals of PI3K-Akt and MAPKs to cause a rise of cell proliferation-associated transcription factor, HSP27. To further verify the effects of the major signals on insulin-promoted cell proliferation, the protein expressions of PI3K and MAPKs were inhibited. It was found that the suppressions of PI3K and ERK signals can attenuate insulin-induced proliferation. Furthermore, insulin activated by PI3K-Akt pathway caused an increase of cell proliferation-related protein expression (e.g. phosphorylation of GSK3β and mTOR) to increase the level of cell cycle-related protein cyclin D1 and to decrease c-Myc expression. However, insulin also stimulated the expression of p53 protein, suggesting that p53 has a feedback regulation to stimulate a dramatic increase, leading to inhibition of cell proliferation. The results indicated that CK can significantly reduce the migration ability of the insulin-induced HCT 116 cells, and it slightly reduced the effect of cell proliferation and anchorage-independent growth. In conclusion, insulin can activate the downstream molecules through IRS-1 signal and increase the expression of PI3K-Akt and MAPKs, which eventually result in the effects of cell proliferation and cell cycle-related protein and enhance cell proliferation and metastasis of CRC. Therefore, it is suggested that ginsenoside CK has the potential to reduce the effects of insulin-induced cancer progression.