Somatostatin elevates topoisomerase II alpha and enhances the cytotoxic effect of doxorubicin on gallbladder cancer cells.
BACKGROUND
Gallbladder cancer is a common and lethal digestive malignancy which is nonsensitive to routine chemotherapy. Doxorubicin (DOX) is one of the major chemotherapeutic drugs for patients with gallbladder cancer. We tried to evaluate if combined use of somatostatin (SST) and DOX could have synergistic effect in the treatment of gallbladder cancer.


METHODS
Cells from the human gallbladder cancer cell line GBC-SD were treated with SST. Cell cycle analysis was determined by flow cytometry. Western blot analysis was performed to determine the protein levels of topoisomerase IIalpha (Topo IIalpha) after SST treatment. RT-PCR was utilized to detect SST receptors in GBC-SD cells. Finally, the chemotherapeutic effect of DOX combined with SST treatment on cellular growth was measured by MTT assay.


RESULTS
SST could induce cell cycle arrest in S phase and upregulate Topo IIalpha expression in GBC-SD cells. GBC-SD cells expressed all 5 subtypes of SST receptors. Finally, combined use of DOX with SST had a synergistic cytotoxic effect on GBC-SD cells.


CONCLUSIONS
SST, a naturally occurring, nontoxic compound, may represent a novel adjuvant chemotherapeutic agent for patients with gallbladder cancer.
Quan
Z W
ZW
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China. zhiwquan@yahoo.com.cn
Yue
J N
JN
Li
J Y
JY
Qin
Y Y
YY
Guo
R S
RS
Li
S G
SG
D000951:Antigens, Neoplasm / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004317:Doxorubicin / Q000633:toxicity*; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D015854:Up-Regulation / Q000187:drug effects
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D059005:Topoisomerase II Inhibitors; D013004:Somatostatin; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II