The synergistic inhibitory effect of somatostatin-doxorubicin co-treatment on gallbladder carcinoma.
BACKGROUND
Gallbladder cancer is the most common billiary tract malignancy and carries a very poor prognosis. Somatostatin was recently shown to play an important role in the development of various tumors. In the current study, we evaluated the effect of doxorubicin on the chemosensitivity of gallbladder cancer cells and xenograft growth after treatment with somatostatin.


METHODS
Twenty-four hours after somatostatin treatment, doxorubicin was gradually added and the growth curve of gallbladder cancer cells was determined. Exponential-phase gallbladder cancer cells were treated with doxorubicine or co-treated with doxorubicine and somastatine and the respective IC50 values were determined. In addition, the inhibitory effect on the growth of gallbladder cancer xenograft on nude mice was evaluated using the same treatments as those described above.


RESULTS
Treatment of gallbladder cancer cells with somatostatin led to a block in the cell cycle at the S phase. Growth inhibition of gallbladder cancer cells by doxorubicin was concentration-dependent (P < 0.05). However, upon co-treatment with doxorubicin and somatostatin, the IC50 value significantly decreased as compared to that of cells treated with doxorubicine alone (P < 0.05). Interestingly, treatment with either doxorubicin or somatostatin did not significantly inhibit xenograft growth on nude mice, in contrast to a co-treatment with both drugs (P < 0.05).


CONCLUSIONS
Somatostatin most likely sensitizes the chemotherapeutic effect and diminishes the cytotoxicity of doxorubicin in a gallbladder cancer cell line and in mouse gallbladder cancer xenografts.
Li
Ji-Yu
JY
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China. lee_jiyu@hotmail.com <lee_jiyu@hotmail.com>
Quan
Zhi-Wei
ZW
Zhang
Qiang
Q
Liu
Jian-Wen
JW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D013004:Somatostatin / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014183:Transplantation, Heterologous
D013004:Somatostatin; D004317:Doxorubicin