Abstract: AIM: To explore the effect of OCTN2 gene polymorphism on the expression and function of OCTN2, as well as the sensitivity of SW480 cells to oxaliplatin.  METHODS: Four mutations of OCTN2 (F17L, E317K, S467C and P478L) transfected cell lines were constructed. Real-time RT-PCR and Western blot were used to detect the levels of OCTN2 mRNA and protein. The content of oxaliplatin was detected by HPLC. MTS assay was used to detect cell viability. RESULTS: The expression level of all mutant OCTN2 mRNA and protein was not significantly different from that of wild-type OCTN2. Oxaliplatin uptake experiments showed that there was no significant difference in Vmax and Km values between E317K and S467C cells (P>0.05), the Vmax of F17L decreased to 66.4% and Km value increased to 120.3%; the Vmax of P478L increased to 132.6%, and the value of Km decreased to 82.2%, and there were significant differences (P<0.05). The cell activity test showed that the IC50 value of all overexpressed OCTN2 cells decreased significantly. Compared with SW480-OCTN2 transfected cell lines, IC50 values of SW480 cells without transfection and F17L cell lines were up to 175% and 147%, while P478L cells decreased to 76.9%, which had significant differences (P<0.05). The IC50 value of E317K and S467C did not change significantly (P>0.05). CONCLUSION: The OCTN2 transporter gene F17L and P478L mutations can alter the uptake of oxaliplatin by OCTN2 transporter, thereby affecting the sensitivity of OCTN2-stably expression cell line to oxaliplatin.

Key words: colorectal cancer, oxaliplatin, chemotherapeutic sensitivity, OCTN2 transporter