Curcumin combining with si-MALAT1 inhibits the invasion and migration of colon cancer SW480 cells

Abstract

To study the effect of small interfering RNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) combining with curcumin on the invasion and migration abilities of human colon cancer SW480 cells, and to explore the involved molecular mechanism. The recombinant lentiviral vector expressing si-MALAT1 was constructed, and its titer was determined by gradient dilution method. The colon cancer SW480 cells with stable expression of si-MALAT1 was established, followed by treatment with curcumin at different concentrations. The effect of curcumin or si-MALAT1 alone and the combination of the two on the cell activity was detected by MTT assay. The cell invasion and migration abilities were detected by transwell and scratch-wound assay. The relative expression level of MALAT1 was detected by RT-qPCR. The protein expression was determined by Western blot analysis. The IC50 of curcumin alone was 77.69 µmol/L, which was 51.17 mol/L when combined with curcumin and random sequence. The IC50 of curcumin was 30.02 µmol/L when combined with si-MALAT1. The increased susceptibility multiples was 2.58. The wound healing rates were 30.9% and 67.5% after treatment with si-MALAT1 combined with curcumin for 24 hrs and 48 hrs, respectively. The numbers of invasion cells were 200±12, 162±13, 66±8, 53±4 and 16±3 after treatment with si-MALAT1 combined with curcumin for 48 hrs. The relative expression level of lncRNA-MALAT1 in the curcumin group was 68%, and the relative expression level of lncRNA-MALAT1 in si-MALAT1group was 56%, and that for the combination treatment group was about 21%. The protein expression levels of β-catenin, c-myc and cyclinD1 were significantly down-regulated upon treatment with certain concentration of si-MALAT1 alone or combined with curcumin.si-MALAT1 could significantly inhibit the invasion and migration of SW480 cells by enhancing the sensitivity of SW480 cells to curcumin. The mechanism involved mignt be related to the down-regulation of β-catenin, c-myc and cyclinD1 proteins.

Therapeutic Effects of Polyphenols on the Treatment of Colorectal Cancer by Regulating Wnt β-Catenin Signaling Pathway

“…Moreover, the progression of EMT was inhibited due to an overexpression of E-cadherin and downregulation of vimentin, as well as inhibition in tumor metastasis due to a significant downregulation in the expression of CXCR4 [ 92 ]. In addition to CUR's anticancer activity in metastasis and invasion of CRC cells, the combination of CUR with siRNAs to mediate restoration in the overexpression of select target genes may also potentially inhibit metastasis and invasiveness of CRC cells [ 93 ]. Along these lines, findings from a previous study demonstrated that combination of CUR with an siRNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) can significantly suppress the migration and invasion of SW480 cells via downregulation in the expression levels of c-Myc, ββ -catenin, and cyclin D1, which is mediated by inactivation of the Wnt ββ -catenin cascade.…”

“…Along these lines, findings from a previous study demonstrated that combination of CUR with an siRNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) can significantly suppress the migration and invasion of SW480 cells via downregulation in the expression levels of c-Myc, ββ-catenin, and cyclin D1, which is mediated by inactivation of the Wnt ββ-catenin cascade. is would suggest that si-MALAT1 can potentially increase the sensitivity of SW480 cells to CUR [93]. One of the most effective pathological processes for increasing the malignant nature of CRC is EMT, which plays a crucial role in promoting metastasis and invasion of human CRC cells [94].…”