Abstract | BACKGROUND: MATERIALS AND METHODS: LS174T and HT-29 which are KRAS and BRAF mutant HER-2-positive colon cancer cells were used in this study. Cells were first treated with T-DM1; cetuximab and trastuzumab were applied for comparison, the effect of drug sensitivity was determined. Cells were then transfected with plasmid to overexpress HER-2 or the endocytic protein, caveolin-1 or furthermore pretreated with metformin to examine the effect of T-DM1 efficacy. Finally, a xenograft mouse model was used to evaluate the drug efficacy in vivo. RESULTS: The results showed that T-DM1 had better inhibitory effect than cetuximab and trastuzumab on LS174T and HT-29 cells. HER-2 or caveolin-1 overexpression with plasmid in the cells to increase T-DM1 recognition or internalization can increase the sensitivity to T-DM1. When cells were pretreated with metformin, caveolin-1 expression was induced and promoted T-DM1 uptake and enhanced cell toxicity. In xenograft mouse model, combined treatment of T-DM1 and metformin had apparent inhibitory effect on subcutaneous tumour growth. CONCLUSION: The results of this study suggested that T-DM1 has potential in the treatment of HER-2-positive colon cancer cells, and application of metformin has therapeutic benefits during T-DM1 treatment.
|
Authors | Yuan-Chiang Chung, Hsi-Hsiung Chiu, Wan-Chen Wei, King-Jen Chang, Wei-Ting Chao |
Journal | European journal of clinical investigation
(Eur J Clin Invest)
Pg. e13255
(Apr 29 2020)
ISSN: 1365-2362 [Electronic] England |
PMID | 32350854
(Publication Type: Journal Article)
|
Copyright | © 2020 Stichting European Society for Clinical Investigation Journal Foundation. |