Effect of interleukins response to ECM-induced acquisition of drug resistance in MCF-7 cells.
OBJECTIVE
To examine the effect of various components of extracellular matrix (ECM) on acquisition of drug resistance to taxol and camptothecin by breast carcinoma cell line MCF-7.


METHODS
Cancer cells were cultured on bovine serum albumin (BSA), vitronectin (VN), fibronectin (FN), collagen type I (COL-I), or Matrigel-coated plates with or without taxol (paclitaxel) or camptothecin treatment. The effect of anticancer drugs on cell growth was accessed by XTT assay, and the alterations of cellular morphology were examined by phase contrast microscopy. Immunofluorescence study was performed using monoclonal anti-beta-tubulin antibody.


RESULTS
All cell lines showed a significant decrease in cell survival when treated with anticancer drugs without components of ECM, whereas survival rates of Caco-2, MCF-7 and NCI-H292 were significantly increased when cells were cultured on COL-I- and Matrigel-coated dishes after treatment with paclitaxel or camptothecin. MCF-7 cells showed and maintained a colony formation when cultured on the COL-I- and Matrigel-coated dish. Moreover, cytotoxicity (IC50) was decreased by taxol (paclitaxel) or camptothecin treatment during colony formation in MCF-7 cells, suggesting that morphological changes could increase survival of cells treated with anticancer drugs. Thick circumferential bundles of microtubules around the periphery of the cells and chromatin condensation was not observed for MCF-7 cells on COL-I- and Matrigel-coated dishes treated with paclitaxel. To confirm this, spheroid cells were prepared, and we found that cytotoxicity was decreased for these cells, and significantly increased when cells were co-cultured on Matrigel- or COL-I-coated upper wells. The effect of anticancer drugs on cell survival was efficiently inhibited by interleukin-6 (IL-6) and interleukin-8 (IL-8).


CONCLUSIONS
Present results suggested that not only integrin-ECM interactions but also other factors such as IL-6and IL-8secreted by cancer cells, cultured on COL-I and Matrigel dishes, are involved in the acquisition of drug resistance by MCF-7.
Ohbayashi
M
M
Department of Clinical Pharmacy, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan.
Yasuda
M
M
Kawakami
I
I
Kohyama
N
N
Kobayashi
Y
Y
Yamamoto
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002166:Camptothecin / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology
D000970:Antineoplastic Agents; D007378:Interleukins; D017239:Paclitaxel; D002166:Camptothecin