Anticancer activity of genistein on implanted tumor of human SG7901 cells in nude mice.
OBJECTIVE
To investigate genistein-induced apoptosis of implanted tumors of SG7901 cells in nude mice, and the relationship between this apoptosis and expression of Bcl-2 and Bax.


METHODS
Establishing a transplanted tumor model by injecting human SG7901 cells into subcutaneous tissue of nude mice. Genistein (0.5, 1 and 1.5 mg/kg) was directly injected adjacent to the tumor, six times at 2-d intervals. Then, changes in tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphological alterations by transmission electron microscopy (TEM), measured the apoptotic rate by the TUNEL staining method, and detected the expression of apoptosis-regulated gene Bcl-2 and bax by immunohistochemical staining and RT-PCR.


RESULTS
Genistein 0.5, 1 and 1.5 mg/kg significantly inhibited carcinoma growth when it was injected near the tumor by 10.8%, 29.9% and 39.6%, respectively. Genistein induced implanted tumor cells to undergo apoptosis, with apoptotic characteristics seen by TEM. The apoptosis index was increased progressively with increasing genistein dose (28.9%+/-1.2%, 33.8%+/-1.6% and 37.7%+/-1.2%). The positive rate of Bcl-2 protein was decreased progressively (11.9%+/-0.9%, 5.9%+/-0.7% and 4.2%+/-0.6%), and the positive rate of bax protein was increased progressively (0.9%+/-1.7%, 24.9%+/-0.8% and 29.6%+/-1.7%) by immunohistochemical staining, with increasing dose of genistein. The density of Bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time by RT-PCR.


CONCLUSIONS
Genistein was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated by down-regulation of the apoptosis-regulated gene Bcl-2 and up-regulation of apoptosis-regulated gene bax.
Zhou
Hai-Bo
HB
Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
Chen
Jin-Ming
JM
Cai
Jian-Ting
JT
Du
Qin
Q
Wu
Chan-Ni
CN
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D016588:Anticarcinogenic Agents; D019833:Genistein