RhoB as a novel molecular target for chemotherapy of colorectal cancer


Year:

Session type:

Theme:

Maria Kopsida1
1Linkoping University

Abstract

Background

The type of therapy for colorectal cancer (CRC) depends on the tumour location and stage. Although chemotherapy remains the mainstay of curative therapies for advance CRC cancer, the rate of distant metastasis is still around 30%. Therefore, there is a clinical need for novel biomarkers to monitor treatment response. RhoB, as the distinct member of Rho superfamily, attracts growing interests, while its expression has been shown altered in several cancer types and emerging evidence supports that RhoB stimulates cell motility, migration, and promotes cancer metastasis, indicating its complex and controversial role in cancer.

Method

Based on the above findings, we aim to explore whether RhoB is related to chemotherapy in CRC, by using human CRC cell lines, zebrafish embryo models and CRC patients. RhoB knockout and overexpressed cell lines were generated via CRISPR and used along with SW480 and HTC116 cell lines for cell proliferation studies.

Results

WST-1 assay was used to examine the cytotoxic action of 5-fluorouracil and oxaliplatin, which have shown potent anticancer activity against our selected panel of cell lines. IC50 values were determined and the concentrations observed were used to investigate the role of RhoB with regards to cell migration, which is inhibited after 72 hour treatment in RhoB knockout cell lines. Caspase-3 activity and autophagy were induced after drug treatment, suggesting that RhoB inhibition can potentially lead to Caspase-3-dependent apoptosis. Furthermore, we developed embryonic zebrafish models for examining the effects of chemotherapy on early stages of tumour cell invasion and dissemination in vivo. Moreover, the RhoB expression was examined among 400 patients that had received preoperative radiotherapy, chemotherapy or had surgery alone

Conclusion

Differential expression of RhoB changes the response to chemotherapy in CRC. Thus, RNA sequencing will be employed to further reveal interacting pathways and the importance of RhoB as a novel target for CRC treatment.