Fig. 6
Targeting circPLPP4 in vivo retards CDDP resistant OC. A-C In vivo luminescent imaging of intraperitoneally implanted A2780 CDDP -luci or A2780 CDDP-luci-ASO-circPLPP4#1 cells in 4–6 weeks-old female BALB/c nude mice treated with PBS or CDDP (5 mg/kg) for three times per week upon the luminescence signal reached 2 × 107 p/sec/cm2/sr. Luminescence intensity ranges from low (blue) to high (red). Tumor burdens were quantified by total photon flux (p/s). D PIK3R1, γH2AX, cleaved caspase-3 and BRCA1 expression levels are examined in representative xenograft tumors by IHC (Left). Quantification of the IHC scores of PIK3R1, γH2AX, cleaved caspase-3 and BRCA1 expression levels (Right). E–H Flow Chart of A2780-CDX-CR (CDDP resistant) model construction. The first CDX generation was constructed in 4–6 weeks-old female BALB/c nude mice and treated with CDDP (5 mg/kg, three times per week). Twelve weeks later, the most resistant xenograft was disaggregated and implanted subcutaneously into 4–6 weeks-old female BALB/c nude mice as the second CR -CDX. Four weeks after implantation, the second CR -CDX mice were treated with CDDP (5 mg/kg, three times per week) and injected via tail vein with ASOs-targetting circPLPP4 or its negative control twice a week. Mice were euthanized when the experiments were finished. The subcutaneous tumor size was measured and recorded every 3 days using the Vernier caliper as follows: tumor volume (mm3) = (L × W2)/2, where L is the long axis and W the short axis. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns indicates no significance