Albumins / pharmacology* ; Animals ; Antinematodal Agents / pharmacology* ; Cisplatin / pharmacology* ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm* ; Female ; Humans ; Mice, Nude ; Paclitaxel / pharmacology* ; Time Factors ; Tumor Burden / drug effects ; Uterine Cervical Neoplasms / drug therapy* ; Uterine Cervical Neoplasms / pathology ; Xenograft Model Antitumor Assays
Keywords
Cervical cancer ; PDOX ; cispatinum ; drug response ; nab-paclitaxel ; nude mice ; patient-derived othotopic xenograft
Abstract
Background: Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective.
Materials and methods: Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX.
Results: H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors.
Conclusion: The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.