Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells

Yan Shi Guo, Gui Fang Jin, Clifford W. Houston, James C. Thompson, Courtney Townsend

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Insulin-like growth factor-I (IGF-I) is known as a potent mitogen for a variety of cell types, including colon cancer cell lines. The objective of this study was to determine the effect of IGF-I on cell death induced by cytotoxic agents actinomycin D (Act-D), lovastatin (LOV), and doxorubicin (DOX) in the MCLM mouse colon cancer cell line, and the mechanisms involved. Subconfluent monolayer MCLM cells were treated with IGF-I (25 ng/ml) for 12 h in serum-free media. Various concentrations of cytotoxic agents then were added to the cells that were incubated continually at 37°C for 24 h. Cell survival was determined with the MTT (3-[4-5-dimenthylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, which assesses mitochondrial function in living cells. The mRNA expression for multidrug resistance gene-I (mdr-I), c-H-ras, and manganese superoxide dismutase (MnSOD) in cells treated with IGF-I was examined by Northern blot or RNase protection assays. The levels of p-glycoprotein, a drug efflux pump encoded by the mdr-I gene, were assessed by Western immunoblotting. Results demonstrated that 1) IGF-I significantly inhibited the cell death and apoptosis of MCLM cells treated with Act-D, LOV, or DOX; 2) IGF-I increased mRNA expression for mdr-I, c-H-ras, and MnSOD; 3) the p-glycoproteins in cells treated with IGF-I or stably transfected with c-H-ras were elevated when compared with control. These results suggest that IGF-I protects MCLM cells against death induced by cytotoxic agents; this acquired drug resistance may be mediated by multiple mechanisms, including promoting expression of mdr-I, c-H-ras, and MnSOD; whereas, the p-glycoprotein level stimulated by IGF-I may result partly from the increase of c-H-ras in the cells.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalJournal of Cellular Physiology
Volume175
Issue number2
DOIs
StatePublished - May 1998

Fingerprint

Multiple Drug Resistance
Insulin-Like Growth Factor I
Colonic Neoplasms
Cells
MDR Genes
Genes
Cytotoxins
Cell death
Superoxide Dismutase
Lovastatin
Glycoproteins
Cell Death
Dactinomycin
Doxorubicin
Assays
Cell Line
Messenger RNA
Serum-Free Culture Media
Ribonucleases
Bromides

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. / Guo, Yan Shi; Jin, Gui Fang; Houston, Clifford W.; Thompson, James C.; Townsend, Courtney.

In: Journal of Cellular Physiology, Vol. 175, No. 2, 05.1998, p. 141-148.

Research output: Contribution to journalArticle

Guo, Yan Shi ; Jin, Gui Fang ; Houston, Clifford W. ; Thompson, James C. ; Townsend, Courtney. / Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. In: Journal of Cellular Physiology. 1998 ; Vol. 175, No. 2. pp. 141-148.
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