[Influence of oxaliplatin combined with LCP on proliferation and apoptosis of colon cancer cell line HT29].
OBJECTIVE
To study the effects of oxaliplatin combined with low-molecular-weight citrus pectin (LCP) on cell proliferation and apoptosis in human colon carcinoma cell line HT29 in vitro.


METHODS
Effects of oxaliplatin alone and oxaliplatin combined with LCP on HT29 cells proliferation were determined by MTT. Coefficient of drug interaction (CDI) was calculated. Influence of oxaliplatin alone and oxaliplatin combined with LCP on HT29 cell apoptosis was determined by fluorescence activated cell sorting (FACS). Protein expression change of procaspase-3, 8, 9, PARP was examined by Western blotting.


RESULTS
Both oxaliplatin alone and oxaliplatin combined with LCP could suppress HT29 cell proliferation in both dose- and time-dependent manner. The inhibitory effect of oxaliplatin combined with LCP on HT29 cell proliferation was more significant (P<0.01) with a CDI less than 1. FACS analysis showed that oxaliplatin alone and combination therapy could increase the apoptosis proportion of HT29 cells. After the drug treatment for 6, 24, and 48 hours, the apoptosis rate of oxaliplatin alone group was (9.76±0.47)%, (20.45±0.74)%, (28.70±3.29)%, and apoptotic rate of the combination group was (20.63±0.69)%, (34.35±1.02)%, (49.47±3.04)%, respectively, which was significantly higher as compared to oxaliplatin alone (P<0.01). Both oxaliplatin alone and combination therapy down-regulated expressions of procaspase-3, 9, and PARP protein. Procaspase-3, 9, PARP protein expression in combination group decreased more significantly, while procaspase-8 expression was not significantly different between the two groups.


CONCLUSIONS
LCP can enhance the ability of oxaliplatin to inhibit cell proliferation and induce apoptosis, which may be associated with the activation of mitochondrial apoptosis pathway.
Department of Gastrointestinal Surgery, Guangzhou Medical College, Guangzhou, China.
Wei-qun
WQ
Lu
Feng
F
Wang
Hai-ying
HY
Liu
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D010368:Pectins / Q000494:pharmacology*
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010368:Pectins