[Effects of lovastatin on proliferation and gap junctional intercellular communication of human breast cancer cell MCF-7].
OBJECTIVE
Lovastatin,an inhibitor of endogenous cholesterol biosynthesis,has been widely used in the clinical treatment of hypercholesterolemia.Recently,lovastatin has been paid more attention for its wide-range effects on human cancer cells; however,the detail mechanisms of its anti-cancer effects are not yet understood. This study was designed to investigate the effects of lovastatin on proliferation and gap junctional intercellular communication (GJIC) of MCF-7 human breast cancer cells.


METHODS
After treated with lovastatin at dosages of 4,8,16 micromol/L for 1-3 days,the cell differentiation was examined with nitroblue tetrazolium (NBT) reduction test;the proliferation and distribution of cell cycles were examined with flow cytometry (FCM). Meanwhile,GJIC of MCF-7 cells was observed using the scrape-loading and dye transfer(SLDT) technique.


RESULTS
Lovastatin could inhibit the proliferation of MCF-7 cells significantly and 75.80 percent of cells were inhibited after treated with 16 micromol/L lovastatin for 72 hours (P< 0.05). Meanwhile, lovastatin could arrest MCF-7 cells in the G(0)/G(1) phase of cell cycle and 80 percent of cells were arrested in G(0)/G(1) phase after treated with lovastatin for 72 hours. Furthermore, lovastatin could induce the differentiation of MCF-7 cells (P< 0.01) and up-regulate GJIC in MCF-7 cells. After treated with 16 micromol/L lovastatin for 72 hours, transfer of LY fluorescence could reach 4-5 rows of cells from the scraped line. However, apoptosis in MCF-7 cells was not obvious. All these effects of lovastatin were in a dose-and time-dependent manner.


CONCLUSIONS
It suggests that lovastatin has the capabilities of inhibiting proliferation, arresting MCF-7 cells at G(0)/G(1) phase of cell cycle and inducing differentiation. These effects of lovastatin maybe correlate with lovastatin promoting GJIC function in MCF-7 cells.
Zhou
Yong
Y
Department of Nutrition and Food Hygiene, The Third Military Medical University, Chongqing, 400038, P.R. China. yongz_lee@hotmail.com
Mi
Man-Tian
MT
Zhu
Jun-Dong
JD
Zhang
Qian-Yong
QY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects; D008148:Lovastatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008148:Lovastatin