WCIM 2014 SEOUL KOREA 545
Poster Session
The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
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Synergistic Effects of Simvastatin and Irinotecan Against Colon Cancer Cells
Hyun Joo Jang1, Jung Eun Choi1, Juah Jang1, Se Woo Park1, Dong Hee Koh1, Min Ho Choi1, Sea Hyub Kae1, Jin Lee1
Hallym University Dontan Sacred Heart Hospital, Korea1
Background: Despite the development of novel therapeutic agents, colon cancer is often resistant to chemotherapy regimens. Statin has pleiotropic effects including an- ti-oxidative, anti-infl ammatory or anti-neoplastic effect. We had already investigated that simvastatin induces the apoptosis of colon cancer cells through control of the expression of IGF-1R and IGF-1R signaling pathways. Therefore, we here investigated whether the combination of simvastatin and irinotecan could induce synergistic effect on HT-29 cells with or without resistance to irinotecan.
Methods: Human colon cancer cells (HT-29) were cultured on dishes with or without irinotecan treatment. We performed cell proliferation assay and determined the degree of apoptosis by caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the effi cacy of drug combination.
Results: We fi rst established HT-29 cells with resistance to irinotecan. While the IC50 values of simvastatin and irinotecan in HT-29 cells without resistance to irinotecan were 115.4±0.14 μM (r=0.98) and 62.5±0.18 μM (r=0.98), respectively, the IC50 values of those were 221.9±0.22 μM (r=0.98) and 195.9±0.16 μM (r=0.99) in HT-29 cell with resistance to irinotecan. According to these IC50 values, the results of combinations for the various concentrations of two drugs showed that combined treatment of irinotecan with simvastatin more potently inhibited cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin/irinotecan at 2:1 molar ratio allowed the best synergistic interaction.
Conclusions: Simvastatin could act synergistically with irinotecan for the treatment of colon cancer. This study supports that simvastatin could be one of the potential drugs to overcome irinotecan resistance of colon cancer.
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Autophagy Inhibition Promotes 2’,4’,6’-Tris (Methoxymethoxy) Chalcone (TMMC)-Induced Apoptosis in Colon Cancer
Wen-Yi Jiang1, Hao Jin1, Jin-hua Chi1, Sung Hee Lee1, In Kyeom Hwang2, Minsu Chu3, Geom Seog Seo3
Department of Pharmacy, BK21 Plus Program & Department of Smart Life-Care Convergence, Wonk- wang University, Graduate School, Korea1, Wonkwang University Sanbon Hospital, Korea2, Digestive Disease Research Institute, Wonkwang University College of Medicine, Korea3
Background: Both autophagy and apoptosis are vital process in cancer; however, their functional relationship remains unclear. We previously reported that 2’,4’,6’-tris (methoxymethoxy) chalcone (TMMC), a synthesized chalcone derivative, induced ap- optosis in rat hepatic stellate cells, and reduced infl ammation both in human intestinal epithelial cells and experimental colitis. The aim of this study was to investigate the anti-tumor effects of TMMC on human colon cancer cells (HCT-116).
Methods: TMMC-induced autophagy was confi rmed by acridine orange staining of intracellular acidic vesicles. Autophagy- and apoptosis-related proteins were detected by western blot analysis. Cell apoptosis was measured by caspase-3 activity assay.
Results: TMMC increased accumulation of microtubule-associated light chain 3 (LC3), and enhanced the conversion of LC3-I to autophagosome-associated LC3-II in pres- ence of autophagy inhibitor. TMMC mediated autophagy induced expression of heme oxygenase-1 (HO-1) via phosphorylation of c-Jun N-terminal kinases (JNK). Inhibition of autophagy was enhanced TMMC-induced Poly (ADP-ribose) polymerase (PARP) cleavage and caspase 3 activation.
Conclusions:In this study, we showed that TMMC induces apoptosis in human cancer cells. Pharmacological inhibition of autophagy enhanced TMMC-induced cancer cell death. These fi ndings provide evidence that TMMC can be used as a new therapeutic agent for colon cancer treatment.
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Association Between Functional Constipation and Intake of Dietary Fiber: A Population-Based Study
Ji Yeoun Kim1, Young Jae Byun1, Dong Soo Han1, Youngouk Ro1, Sun Min Kim1, Chang Soo Eun1
Hanyang University Guri Hospital, Korea1
Backgrounds: Patients with functional constipation are often recommended to in- crease dietary fi ber intake and overactive bladder (OAB) may be associated with bowel symptoms. We examined the associations among functional constipation, dietary fi ber intake, and OAB in Korean population cohort.
Methods: This cohort study, using a reliable and valid questionnaire based on the Rome III criteria was performed in Yangpyeong city, Korean community on subjects aged = 40 years between 2011 and 2012. Total, grain, vegetable, fruit and seaweed fi ber intakes were estimated from dietary questionnaires. OAB was defi ned through overactive bladder symptom score. The associations among functional constipation, dietary fi ber intake, and OAB were assessed separately by age and gender.
Results: A total of 1,173 patients were enrolled, with mean age of 62.4±29.0, of which 63% was comprised of women. There were 134 (11.4%) patients with function- al constipation. Total fi ber intake was associated with a signifi cantly lower prevalence of functional constipation in men, not in women. On the contrary, OAB was correlated with functional constipation in elderly women.
Conclusion: Men who consumed high amount of fi ber have a lower prevalence of functional constipation. OAB is associated with functional constipation in elderly women. This population-based study suggest that the pathogenesis of functional con- stipation may be different between men and women.
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Effect of Lactobacillus Gasseri BNR17 in Patients with IBS with Diarrhea on Improvement of Bowel Function
Suk Pyo Shin1, Yunmi Choi1, Won Hee Kim1, Ki Baik Hahm1 Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Korea1
Background: Irritable bowel syndrome (IBS) is a common disorder characterized by chronic and relapsing abdominal pain, distension and altered bowel habits. Lactoba- cillus gasseri BNR17 is a probiotic strain isolated from human breast milk. This study aimed to evaluate the improvement of bowel function in patients with IBS with diar- rhea when consuming this probiotic.
Methods: This study was designed as a randomized, double blind, placebo-controlled study with parallel groups to assess the effect of consumption of Lactobacillus gas- seri BNR17. Individuals meeting the ROME III criteria for IBS and functional diarrhea, between 20-55 years of age were included and randomized to consume Lactobacillus gasseri BNR17 containing capsules or placebo capsules for 8weeks.
Results: 61 patients were enrolled and 51 patients were included for analysis. When analyzing IBS-QOL questionnaire, symptoms were signifi cantly improved at week 8 in both Lactobacillus gasseri BNR17 group and placebo group, but there was little difference between the two groups. We also analyzed the colon transit time. In BNR 17 group, the mean transit time was 5.4hours at week 0 and 19.2hours at week 8 (p=0.0464). Whereas in placebo group, the mean transit time did not show the dif- ference between at week 0 and week 8 (8.4hours at week 0, 13.2hours at week 8, p=0.2762).
Conclusions: Lactobacillus gasseri BNR17 improved bowel function based on both IBS-QOL questionnaire and Colon transit time study in patients with IBS with diarrhea.
