Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

نویسندگان

  • Hyun Joo Jang
  • Eun Mi Hong
  • Juah Jang
  • Jung Eun Choi
  • Se Woo Park
  • Hyun Woo Byun
  • Dong Hee Koh
  • Min Ho Choi
  • Sea Hyub Kae
  • Jin Lee
چکیده

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4 ± 0.14 μM (r = 0.98) and 62.5 ± 0.18 μM (r = 0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9 ± 0.22 μM (r = 0.98) and 195.9 ± 0.16 μM (r = 0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2 : 1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Protective role of Lactobacillus plantarum A7 against irinotecan-induced genotoxicity

Objective: Irinotecan is a botanical derivative and an anti-cancer drug with cytotoxic and genotoxic effects. The present study evaluated the effect of Lactobacillus plantarum A7 on the genotoxic activity of irinotecan in a hepatocellular carcinoma cell line (HepG2) by comet assay. Materials and Methods: HepG2 were incubated with irinotecan (100 µM), heat-killed cells (0.025 µg/ml) + irinotecan...

متن کامل

Encapsulation of irinotecan in polymeric nanoparticles: Characterization, release kinetic and cytotoxicity evaluation

Objective(s): Irinotecan is a potent anti-cancer drug from camptothecin group which inhibits topoisomerase I. Recently, biodegradable and biocompatible polymers such as poly lactide-co-glycolides (PLGA) have been considered for the preparation of nanoparticles (NPs). Materials and Methods: In this study, irinotecan loaded PLGA NPs were fabricated by an emulsification/solvent diffusion method to...

متن کامل

Prevention of intestinal toxic effects and intensification of irinotecan's therapeutic efficacy against murine colon cancer liver metastases by oral administration of the lipopeptide JBT 3002.

The induction of severe diarrhea limits the usefulness of the DNA topoisomerase I inhibitor irinotecan (CPT-11) in the treatment of advanced colon cancer. We investigated whether oral administration of the new synthetic bacterial lipopeptide, JBT 3002, encapsulated in phospholipid liposomes could prevent damage to the intestinal epithelium and lamina propria and thus allow for the parenteral ad...

متن کامل

Vitamin D Enhances the Efficacy of Irinotecan through miR-627-Mediated Inhibition of Intratumoral Drug Metabolism.

Cytochrome P450 enzyme CYP3A4 is an important drug-metabolizing enzyme, and high levels of tumoral expression of CYP3A4 are linked to drug resistance. We investigated the function of vitamin D-regulated miR-627 in intratumoral CYP3A4 suppression and its role in enhancing the efficacy of chemotherapy. We found that miR-627 targets CYP3A4 and suppresses CYP3A4 expression in colon cancer cell line...

متن کامل

The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells.

Colon cancer represents one of the most common solid tumors in adults. Although 5-fluorouracil (5-FU) and irinotecan have been frequently administered in colon cancer patients, low response rates to these single drug therapies were reported. It is therefore imperative to search for new targeted combination therapies that are effective. In this study, we investigated the anti-cancer effect of sa...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 2016  شماره 

صفحات  -

تاریخ انتشار 2016