Research Paper Volume 13, Issue 10 pp 13405—13420

Inhibition of CXCR2 plays a pivotal role in re-sensitizing ovarian cancer to cisplatin treatment

CXCR2 is a pivotal molecule in OC cellular viability. Clonogenic assays were run to evaluate the role of CXCR2 on OC cellular viability under the follow experimental conditions: i) cells transfected with empty vector (10μM), NC, control; ii) cells transfected with siRNA CXCR2 (10μM) to get the KD models; iii) cells that received cisplatin (5uM); iv) CXCR2 KD cells + cisplatin (5uM); v) cells treated with the CXCR2 antagonist SB225002 (1ug/ml); vi) cells that received combined therapy containing cisplatin (5uM) and SB225002 (1ug/ml). 150 cells of each lineage were plated on 6-well plates. Colonies were stained with crystal violet at D10. (A) Representative figure of the stained plate. The experiment confirmed A2780 sensitivity vs. ACRP resistance to cisplatin. A2780 CXCR2 KD cells were more viable than ACRP CXCR2 KD cells. Moreover, ACRP was more sensitive to SB225002 than A2780. On both cells, there was additive effects with the combined treatment containing cisplatin and siRNA against CXCR2 or cisplatin and SB225002. (B) Graphic representation of the percentage of colonies formed under each experimental condition, clearly reflecting Figure 5A. This experimental approach has proven the pivotal role of CXCR2 in the acquisition of cisplatin chemoresistant phenotype by OC cells. Data were analyzed by two-way ANOVA followed by Bonferroni post-test. *p

Figure 6. CXCR2 is a pivotal molecule in OC cellular viability. Clonogenic assays were run to evaluate the role of CXCR2 on OC cellular viability under the follow experimental conditions: i) cells transfected with empty vector (10μM), NC, control; ii) cells transfected with siRNA CXCR2 (10μM) to get the KD models; iii) cells that received cisplatin (5uM); iv) CXCR2 KD cells + cisplatin (5uM); v) cells treated with the CXCR2 antagonist SB225002 (1ug/ml); vi) cells that received combined therapy containing cisplatin (5uM) and SB225002 (1ug/ml). 150 cells of each lineage were plated on 6-well plates. Colonies were stained with crystal violet at D10. (A) Representative figure of the stained plate. The experiment confirmed A2780 sensitivity vs. ACRP resistance to cisplatin. A2780 CXCR2 KD cells were more viable than ACRP CXCR2 KD cells. Moreover, ACRP was more sensitive to SB225002 than A2780. On both cells, there was additive effects with the combined treatment containing cisplatin and siRNA against CXCR2 or cisplatin and SB225002. (B) Graphic representation of the percentage of colonies formed under each experimental condition, clearly reflecting Figure 5A. This experimental approach has proven the pivotal role of CXCR2 in the acquisition of cisplatin chemoresistant phenotype by OC cells. Data were analyzed by two-way ANOVA followed by Bonferroni post-test. *p<0.05, **p<0.01, ***p<0.001. N=3.