Combination with SN-38 on human colon cancer LoVo cells / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 746-851, 2009.
Article
in Chinese
| WPRIM
| ID: wpr-293061
ABSTRACT
<p><b>OBJECTIVE</b>To observe the anti-proliferation effect of bevacizumab and SN-38 (active metabolite of irinotecan), and investigate the possible mechanisms of these two agents.</p><p><b>METHODS</b>Human colon cancer LoVo cells were cultured under hypoxic conditions. Inhibition of cell proliferation was evaluated by MTT assay. The drug modulation on HIF-1alpha, VEGF, ERK and AKT were assessed by the following assays. The mRNA expression of HIF-1alpha and VEGF were measured by RT-PCR. The protein expression of HIF-1alpha, ERK and AKT were evaluated by Western blot analysis, and VEGF by ELISA assay.</p><p><b>RESULTS</b>Among different combination schedules, Bevacizumab given after SN-38 show most synergistic anti-proliferation effect. Under hypoxic conditions, the expression of HIF-1alpha and VEGF increased as time accumulated, Bevacizumab combined with SN-38 almost completely inhibited the expression of HIF-1alpha and VEGF. Moreover, the MAP kinase pathway was involved in the drug modulation of HIF-1alpha and VEGF.</p><p><b>CONCLUSION</b>These findings suggest the anti-proliferation effect of bevacizumab and SN-38 was schedule-dependent, and the synergistic effect of Bevacizumab and SN-38 was related to drug modulation of the HIF-1alpha and MAP kinase pathway.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Time Factors
/
Camptothecin
/
RNA, Messenger
/
Signal Transduction
/
Cell Hypoxia
/
Colonic Neoplasms
/
Cell Line, Tumor
/
Vascular Endothelial Growth Factor A
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Oncology
Year:
2009
Type:
Article
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