Dr. Weeks’ Comment: First came the innovation in 1946, then the 60 years of clinical experience primarily in Mexico and now science is supporting the use of insulin as a potentiator of chemotherapy.
J Huazhong Univ Sci Technolog Med Sci. 2010 Oct;30(5):631-7. Epub 2010 Nov 10.
Department of Obstetrics and Gynecology, Huazhong University of Science and Technology, Wuhan, China. firstname.lastname@example.org
The effects of insulin or insulin in combination with chemotherapeutic drugs on the proliferation and apoptosis of endometrial carcinoma cells were examined with an aim to determine the efficacy and safety of insulin in endometrial cancer therapy. Ishikawa and Hec-1A cells were treated with insulin and/or paclitaxel. Cell proliferation was assessed by MTT assay. Cell cycle and cell apoptosis were determined by flow cytometry (FCM). Survivin gene expression was detected by RT-PCR. Our results showed that in a certain range of working concentrations and action time, insulin could mildly augment cell proliferation and the percentage of S phase cells in endometrial cancer (Ishikawa/Hec-1A) cells.
Insulin plus paclitaxel (combination group) could significantly inhibit cell proliferation (69.38%±2.32% vs 40.31%±4.52% with Ishikawa; 64.11%±6.33% vs 45.89%±3.27% with Hec-1A) and increase cell apoptosis compared with treatment with paclitaxel alone (paclitaxel group). Survivin gene expression was also significantly decreased in combination group as compared with paclitaxel group.
We are led to conclude that insulin can mildly augment cell proliferation and present chemotherapy sensitivity in endometrial cancer cells. Insulin can be to used safely and efficiently in endometrial cancer therapy.
PMID: 21063847 [PubMed – in process]
Zhonghua Zhong Liu Za Zhi. 2010 Mar;32(3):169-72.
[Article in Chinese]
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
OBJECTIVE: To explore the possibility of use of insulin as a potentiator of 5-Fu to human colon cancer cell lines HCT-8 and HT-29 and study its mechanism.
METHODS: MTT assay was used to examine the inhibition rate of cell growth after treatment with 5-Fu and insulin. Cell cycle was determined by flow cytometry.
RESULTS: Insulin showed an enhancing effect on the chemotherapeutic response of 5-Fu when insulin was applied at a dose of exceeding 0.8 mU/ml 0 approximately 8 h before 5-Fu. Within the range of from 0.8 mU/ml to 8 mU/ml, a higher concentration of insulin gave a higher proportion of inhibited cells. But when the insulin concentration exceeds 8 mU/ml, the proportion became stable as that of 8 mU/ml. Insulin increased the percentage of S phase cells and decreased the percentage of G(1) phase cells (P < 0.01). The percentage of S phase cells reached a peak when the cells were treated with insulin for 6 hours.
CONCLUSION: Insulin can enhance the anticancer toxicity of 5-Fu to human colon cancer cell lines HCT-8 and HT-29 cells. Insulin increases the percentage of S phase cells, which may be one of the main mechanisms of insulin-induced enhancement of anticancer response of cancer cells to 5-Fu chemotherapy.
Acta Pharmacol Sin. 2007 May;28(5):721-30.
Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
AIM: To investigate the effects of insulin on enhancing 5-fluorouracil (5-FU) anticancer functions and its mechanisms in the human esophageal cancer cell line (Eca 109) and human colonic cancer cell line (Ls-174-t).
METHODS: The effect of insulin/5-FU combination treatment on the growth of Eca 109 and Ls-174-t cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. After insulin treatment or insulin/5-FU treatment, cell cycle distribution of both cell lines was analyzed by flow cytometry. Western blot assay was used to assess the expression of caspase-3 and thymidylate synthase (TS). Apoptosis was detected by flow cytometry, DNA fragmentation assay, and terminal transferase dUTP nick end labeling assay (TUNEL). Moreover, the changes of 5-FU uptake after insulin pretreatment were detected by HPLC assay and Western blot analysis.
RESULTS: We found that insulin enhanced the inhibitory effect of 5- FU on cell proliferation when Eca 109 cells and Ls-174-t cells were pretreated with insulin for the appropriate time. Insulin increased the cell number of the S phase and the uptake of 5-FU. Insulin/5-FU treatment enhanced apoptosis of tumor cells and upregulated the expression of cleaved caspase-3 compared with 5-FU treatment. Moreover, insulin/5-FU treatment induced the changes of free TS and the TS ternary complex level compared with 5-FU treatment in Eca 109 and Ls-174-t cells.
CONCLUSION: These data suggest that insulin enhances anticancer functions of 5- FU when it is treated before 5-FU for the appropriate time in human esophageal and colonic cancer cell lines.