Inhibition of pancreatic cancer cell growth by cucurbitacin B through modulation of signal transducer and activator of transcription 3 signaling.
OBJECTIVE
Pancreatic cancer is a serious disease worldwide for its high mortality. Gemcitabine has become the frontline option for the treatment of this disease since its approval. However, resistance to the drug has been on the rise in recent years. Searching for other chemotherapeutic agents therefore has attracted much attention. Cucurbitacin B (CuB) is a member of the triterpenoid family and has shown inhibitory effect on various cancer cells. In this study, we have assessed the effect of CuB on pancreatic cancer cells.


METHODS
The growth of human pancreatic cancer cells (PANC-1) was monitored using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cell cycle distribution and apoptosis were evaluated with fluorescence-activated cell sorter and fluorescent microscopy. Western blot was used to determine the expression of relevant genes including phosphorylated signal transducer and activator of transcription 3 (pSTAT3), STAT3, p53, p21, Bcl-2, survivin, and caspase 3.


RESULTS
Our results showed that CuB can inhibit the growth of PANC-1 cells in a dose- and time-dependent manner, resulting in accumulation of G2/M phase cells and apoptosis. Furthermore, CuB treatment inhibited STAT3 phosphorylation, activated caspase 3, up-regulated the expression of p53 and p21, and down-regulated the expression of Bcl-2 and survivin.


CONCLUSIONS
Our results suggested that CuB may provide an effective regimen for the treatment of pancreatic cancers.
Zhang
Meixia
M
Department of Clinical Pharmacology, China Medical University, 92 Bei'er Rd, Shenyang 110001, China. zhangmeixia@mail.cmu.edu.cn
Sun
Chunyan
C
Shan
Xiaolei
X
Yang
Xiaolin
X
Li-Ling
Jesse
J
Deng
Yihui
Y
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D010545:Peroxides / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000077022:Survivin; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C107489:BIRC5 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D010545:Peroxides; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D000077022:Survivin; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; C041246:cucurbitacin B; D053148:Caspase 3