Effects of Loading TAB2 siRNA and Cisplatin Nano-Liposomes Mediated Macrophage Polarization on Drug Resistance, Proliferation and Metastasis of Ovarian Cancer Cells

Bo Li and Shuping Li

Background and Objective: Tumor cell reduction surgery combined with cisplatin chemotherapy can achieve remission in ovarian cancer (OC) patients, but most patients will experience recurrence. This work investigated the effects of co-loading Small Interfering RNA (siRNA) targeting transforming growth factor-beta activated kinase 1 binding protein 2 (TAB2) and cisplatin in nano-liposomes, mediated by macrophage M2 polarization, on drug-resistant OC cell proliferation and migration. Materials and Methods: Bone Marrow-Derived Macrophage (BMDM) was obtained from mouse bone marrow and interleukin-5 induced M2 polarization of the cells. A cisplatin-resistant OC cell model (ID8/R) was prepared using the cisplatin gradient exposure method. Normal culture was used as the Ctrl group and co-loaded negative control, TAB2 siRNA and cisplatin-loaded nanoliposomes (siNC-DDP-LNP and siTAB2-dDP-LNP) were transfected to detect the activation status of M2 type BMDM. The BMDM-conditioned medium was added and cell proliferation and migration were detected. Results: The prepared siNC-DDP-LNP and siTAB2-DDP-LNP possessed similar circular morphology with a PS of around 100 nm. The siRNA EE was >90% and the drug LC was >0.14 μg/μL. After transfection, the siTAB2-DDP-LNP group showed a great reduction in TAB2 (p<0.05). Following BMDM identification, the M1 type markers (iNOS and TNF-α expression, average fluorescence intensity (FI) of CD80 and CD86) decreased, while the M2 type markers (Arg1 and Mgl1 expression, average FI of CD206 and CD163) increased, with sharp differences (p<0.05). After transfection with BMDM conditioned medium and nano-liposomes, the siTAB2-DDP-LNP group presented greatly increased average FI values of CD80, CD86 and CD40, decreased cell viability and reduced count of migrated cells, exhibiting great differences after comparison (p<0.05). Conclusion: The siTAB2/DDP-LNP effectively activated tumor-associated macrophage polarization, thereby achieving effective killing of drug-resistant OC cells (OCCs).

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