Inhibition of pro-platelet basic protein (CXCL7) induces antineoplastic effects in colorectal cancer cells

Abstract

Background: Colorectal cancer (CRC), a 3^rd leading cause of cancer-related deaths worldwide, is characterized by high metastatic potential and poor survival rates in advanced stages. Pro-platelet basic protein (CXCL7) is a chemokine and plays crucial roles in promoting tumor progression, angiogenesis, immune modulation and metastasis. Elevated CXCL7 expression correlates with increased tumor vascularization, immune cell recruitment, and poor clinical outcomes. This study investigates the potential of targeting CXCL7 to inhibit CRC progression and metastasis related properties.

Methods: The role of CXCL7 in CRC was evaluated by using SW480 (human) and CC531 (rat) cell lines. CXCL7 expression was knocked down using siRNA, and its effects on cell proliferation, colony formation, migration, wound healing and apoptosis were assessed through MTT assays, colony formation assays, migration assays, scratch-healing assays and nuclear staining, respectively. RNA expression levels were analyzed through real-time PCR.

Results: CXCL7 knockdown was achieved significantly at mRNA levels, with a maximum reduction of 76% and 81% in SW480 and CC531 cells, respectively, within 24 hours. This led to reduced cell proliferation, where SW480 cells showed a maximum inhibition of 56% compared to 39% in CC531 cells. Colony formation declined significantly in both cell lines, with a more pronounced effect on large colonies. Migration and scratch healing capacities were reduced by up to 26% in SW480 cells and 67% in CC531 cells, demonstrating impaired motility. Apoptotic markers, including nuclear condensation and fragmentation, were observed after CXCL7 inhibition.

Conclusion: Targeting CXCL7 in CRC reduces tumor cell proliferation, colony formation, migration, and wound healing while inducing apoptosis. These findings highlight CXCL7 as a promising therapeutic target for CRC management and warrant further exploration in clinical settings.