[Study on anticancer effect of dihydroartemisinin on pancreatic cancer].
OBJECTIVE
To investigate the anti-tumor activity of dihydroartemisinin in pancreatic cancer in vitro and in vivo.


METHODS
For cultured cells, cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis stained with Annexin V-FITC/PI. The protein expression in BxPC-3 cells was analyzed by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to dihydroartemisinin. Ki-67 staining and TUNEL assay were used to assess tumor cell proliferation and apoptosis in tumor tissue.


RESULTS
After treatment by dihydroartemisinin in vitro, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and AsPC-1 reached up to (76.2 +/- 3.5)% and (79.5 +/- 2.9)%, and the apoptosis rates were up to (55.5 +/- 3.2)% and (40.0 +/- 3.5)%, the differences were significantly (P < 0.01) compared with control [(2.0 +/- 1.3)% and (0.9 +/- 0.4)%]. Dihydroartemisinin inhibited the growth of pancreatic xenograft tumors in nude mice. The proliferation index and apoptosis index were (49.1 +/- 3.9)% and (50.2 +/- 4.4)% respectively in dihydroartemisinin 50 mg/kg treatment group, compared to those of (72.1 +/- 3.3)% and (9.4 +/- 2.9)% in control, the differences were significantly (P < 0.01). Western blot assay indicated that dihydroartemisinin up-regulates expression of proliferation-associated protein p21(WAF1) and down-regulates expression of PCNA, increases expression of apoptosis-associated protein Bax and decreases expression of Bcl-2 and activates caspase-9 in BxPC-3 cells.


CONCLUSIONS
Dihydroartemisinin exerts anti-tumor activity in pancreatic cancer both in vitro and in vivo by proliferation inhibition and apoptosis induction. Dihydroartemisinin can be used as a potential anti-tumor drug in pancreatic cancer.
Chen
Hua
H
Department of Hepatobiliary and Pancreatic Surgery, the First Clinical College of Harbin Medical University, Harbin 150001, China.
Sun
Bei
B
Pan
Shang-ha
SH
Li
Jun
J
Xue
Dong-bo
DB
Meng
Qing-hui
QH
Jiang
Hong-chi
HC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D037621:Artemisinins; C039060:artenimol