Biglycan (BGN) is overexpressed in cancer stem cells of colon cancer and induces the activation of NF-κB pathway which contributes to the chemotherapy resistance of diverse cancer types. Therefore, we hypothesized that the overexpression of BGN also promoted the development of multiple drug resistance (MDR) in colon cancer via NF-κB pathway. The expression of BGN was bilaterally modulated in colon cancer cell lines HT-29 and SW-480 and the effect of treatments on the cell proliferation and resistance to 5-FU was assessed. Moreover, the role of NF-κB signaling in the BGN-mediated formation of MDR was further investigated by subjecting BGN-overexpressed SW-480 cells to the co-treatment of chemo-agents and NF-κB inhibitor, PDTC. The inhibition of BGN expression decreased the proliferation potential of HT-29 cells while the induction of BGN expression increased the potential of SW-480 cells. BGN knockdown increased HT-29 cells' sensitivity to 5-FU, represented by the lower colony number and higher apoptotic rate. To the contrary, BGN overexpression promoted the resistance of SW-480 cells to 5-FU. The effect of BGN modulation on colon cancer cells was associated with the changes in apoptosis and NF-κB pathways: BGN inhibition increased the expressions of pro-apoptosis indicators and suppressed NF-κB pathway activity while BGN overexpression had the opposite effect. It was also found that the BGN-mediated formation of MDR was impaired when NF-κB pathway was blocked. Findings outlined in the current study showed that BGN contributed to the formation of chemotherapy resistance in colon cancer cells by activating NF-κB signaling.
Keywords: Apoptosis; Biglycan; Colon cancer; Multiple drug resistance; NF-κB.