Influence of neoadjuvant intraarterial infusion chemotherapy on apoptosis and multidrug resistance associated genes of endometrial cancer

Abstract

Objective: Through investigating the influence of neoadjuvant intraarterial infusion chemotherapy (NIAC) on the timing changes of apoptosis, PCNA and multiple drug resistance associated genes of endometrial cancer, to study the mechanism of chemotherapy and to define the best operation time. Methods: Twenty patients were subjected to neoadjuvant consecutive uterine arterial infusion with CDDP 100 mg and ADM 50 mg. The biopsy of endometrial tumor tissues was performed before, immediate after and 1, 2–2+3 w, 3+3–4 w after chemotherapy. Apoptosis index (AI) was estimated by a combination of histologic and TUNEL assays. Proliferative index (PI) was examined by SABC immunohistochemical staining. Expressions of multidrug resistance 1 (MDR1), multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) were detected by reverse transcription polymerase chain reaction (RT-PCR). Results: The AI of endometrial cancer cells immediate after and 1, 2-2+3 w, after chemotherapy were 3.03%, 3.47% and 5.04%, respectively, much higher than that before chemotherapy which was 2.31%. After chemotherapy, AI/PI gradually increased. It was highest in 2-2+3 w, while 3+3-4 w after chemotherapy the AI and AI/PI were both significantly lower than that before chemotherapy. The expression of MDR1, MRP and LRP all decreased temporarily after chemotherapy, while 3+3-4 w after chemotherapy they all increased to levels higher than that before chemotherapy, but the difference were not significant (P>0.05). Conclusion: Neoadjuvant consecutive intra-arterial infusion chemotherapy via uterine artery can inhibit tumor cells proliferation and induce apoptosis effectively. To evaluate the response of intra-arterial chemotherapy the change of apoptosis index and cell proliferation should be analyzed. The most suitable time for the operation is 3 weeks after intra-arterial infusion chemotherapy.