INSULIN-LIKE-GROWTH-FACTOR-1 (IGF-1) ALTERS DRUG-SENSITIVITY OF HBL100 HUMAN BREAST-CANCER CELLS BY INHIBITION OF APOPTOSIS INDUCED BY DIVERSE ANTICANCER DRUGS

In this study, we tested the hypothesis that insulin-like growth facto r-1 (IGF-1) modulates apoptosis in human breast cancer cells, HBL100, induced by diverse chemotherapeutic drugs. IGF-1 increased cell surviv al of HBL100 cells treated with 5-fluorouracil (antimetabolite), metho trexate (antimetabolite), tamoxifen (antiestrogen/antiproliferative), or camptothecin (topoisomerase 1 inhibitor) and after serum withdrawal . Elevated cell survival was not due to an increase in cell proliferat ion by IGF-1, but rather to an inhibition of apoptosis. Evidence for d eath by apoptosis was supported by cellular morphology and DNA fragmen tation. There were no changes observed in Bcl-2 protein or bax mRNA le vels. Extracellular matrix (ECM) is known to influence the apoptotic r esponse of cells; therefore, the antiapoptotic effect of IGF-1 on brea st cancer cells was examined using different ECMs: laminin, collagen I V, or Matrigel. IGF-1 protected cells from apoptosis induced by methot rexate on all ECMs tested, providing the first evidence that IGF-1 pro tects against apoptosis in three-dimensional culture systems. These da ta provide the rationale to search for drugs that lower serum IGF-1 in an effort to improve the efficacy of chemotherapeutic drugs for the t reatment of breast cancer.