Ganoderma lucidum inhibits proliferation of human ovarian cancer cells by suppressing VEGF expression and up-regulating the expression of connexin 43.
BACKGROUND
Ganoderma lucidum (G. lucidum, Reishimax) is an herbal mushroom known to have inhibitory effect on tumor cell growth. However, the molecular mechanisms responsible for its anti-proliferative effects on the ovarian cancer have not been fully elucidated.


METHODS
Human ovarian cancer cells HO 8910 (HOCC) and human primary ovarian cells (HPOC) were treated with G. lucidum. Effects of G. lucidum treatment on cell proliferation were studied by MTT assay. The expression of vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) were measured by immunohistochemistry and real time polymerase chain reaction. To study the molecular mechanism of CX43 mediated anti-tumor activity, small interference RNA (siRNA) was used to knockdown Cx43 expression in HOCC.


RESULTS
G. lucidum treatment resulted in reduced proliferation of HOCC. Inhibition of proliferation was accompanied by a decrease in VEGF expression and increase in Cx43 expression in the cancer cells. The extent of immune-reactivity of Cx43 or VEGF in cancer cells were correlated with the concentrations of G. lucidum used for treatment. Furthermore, knockdown of Cx43 expression in HOCC abrogated the effect of G. lucidum on cell proliferation without alteration of G. lucidum-induced attenuation of VEGF expression.


CONCLUSIONS
G. lucidum inhibits ovarian cancer by down-regulating the expression of VEGF and up-regulating the downstream Cx43 expression. G. lucidum may be a promising therapeutic agent for the treatment of ovarian cancer.
Department of Obstetrics and Gynecology, The Affiliated Shengjing Hospital, China Medical University, 36 Sanhao Street, Heping district, Shenyang 110004, People's Republic of China. daishy2014@163.com.
Shuyan
S
Dai
Jingjing
J
Liu
Xiaofei
X
Sun
Ning
N
Wang
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020940:Reishi / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D018031:Connexin 43; D004365:Drugs, Chinese Herbal; D042461:Vascular Endothelial Growth Factor A