Treatment mechanism of matrine in combination with irinotecan for colon cancer

Abstract

The inhibitory effect of matrine (MA) was studied in combination with irinotecan (CPT-11) on proliferation of human colon carcinoma cell line HT29. We also explored the mechanism of cell apoptosis induction in HT29. HT29 cells were treated with different concentrations of MA and CPT-11 alone and in combination. The growth inhibition in HT29 cells was evaluated using MTT assay. Apoptosis was detected using AV-PI double staining flow cytometry. Transmission electron microscopy was used to detect structural changes in cells. Topoisomerase (TOPO) I, Bax and Caspase-3 expression levels were evaluated using western blot analysis. MA and CPT-11 alone and in combination, inhibited the proliferation of HT29 cells, whereas the combination treatment exhibited higher inhibitory effect (P<0.01). This suggests the existence of synergistic cytotoxicity. Compared with each treatment alone, the combination treatment caused more significant damage to cell structure, and caused a significantly higher apoptosis rate (P<0.01). Additionally, the combination treatment increased TOPO I, Bax and Caspase-3 expression levels (P<0.01). In conclusion, MA in combination with CPT-11 synergistically inhibited HT29 cell proliferation and induced apoptosis in these cells. The mechanism may be related to upregulation of the TOPO I, Bax and Caspase-3 protein expression.

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

“…Another study found that MT and cisplatin synergistically suppressed the growth of urothelial bladder cancer cells (EJ, T24, BIU and 5637 cells) by inhibiting the VEGF/PI3K/Akt signaling pathway (Liao et al, 2017). Moreover, the protein expression levels of topoisomerase (TOPO) I, Bax, and caspase-3 were up-regulated in HT29 cells treated with a combination of MT and irinotecan (Duan et al, 2017). Rong et al reported that MT combined with platinum-based doublet chemotherapy (PBDC) had a lower adverse reaction rate, higher response rate (RR), disease control rate (DCR) and mean survival time (MST), and better quality of life (QOL) than PBDC alone (Rong et al, 2015).…”

“…Another study found that MT and cisplatin synergistically suppressed the growth of urothelial bladder cancer cells (EJ, T24, BIU and 5637 cells) by inhibiting the VEGF/PI3K/Akt signaling pathway ( Liao et al., 2017 ). Moreover, the protein expression levels of topoisomerase (TOPO) I, Bax, and caspase-3 were up-regulated in HT29 cells treated with a combination of MT and irinotecan ( Duan et al., 2017 ). Rong et al.…”

Matrine promotes apoptosis in SW480 colorectal cancer cells via elevating MIEF1‐related mitochondrial division in a manner dependent on LATS2‐Hippo pathway

“…Several studies have found that the matrine inhibits the progression of liver cancer (Wang et al, ), thyroid tumor (Abeysuriya, Lockley, Robinson, & Postnova, ), lung tumor (Angelova et al, ), glioblastoma (Boga et al, ), prostate cancer, and pancreatic cancer (Coverstone et al, ). Although many careful studies have been performed to verify the anticancer action of matrine in CRC (Duan et al, ; Fan et al, ), its cancer‐killing mechanisms are not fully understood.…”

Recent Advances in Herbal Medicines for Digestive System Malignancies

“…The anti-tumor effect of gemcitabine on gallbladder carcinomas can be enhanced by suppressing the NF-κB pathway (Yang et al, 2012 ), which suggests that oxymatrine may increase efficacy of chemotherapeutic drugs by down-regulating the NF-κB pathway. Duan et al found that the percentage of colon cancer cells suppressed with a combination of matrine and irinotecan (CPT-11), a first-line drug for colon cancer, was higher than that with either matrine or irinotecan alone, which might be associated with up-regulation of Topoisomerase (TOPO) I, Bax and Caspase-3 (Duan et al, 2017 ). The results suggested that matrine has a synergistic effect with irinotecan in the treatment of colon cancer.…”