siAKR1C3@PPA complex nucleic acid nanoparticles inhibit castration-resistant prostate cancer in vitro

• Published in: Frontiers in oncology Vol. 12; p. 1069033
• Main Authors: Cui, Xiaoli, Yao, Zhou, Zhao, Tianyu, Guo, Jiahui, Ding, Jipeng, Zhang, Siwei, Liang, Zuowen, Wei, Zhengren, Zoa, Alexis, Tian, Yuantong, Li, Jing
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.12.2022
• Subjects: 4D label-free proteomics; AKR1C3; castration-resistant prostate cancer; nucleic acid nanoparticles; Oncology; PAMAM (G5) dendrimers; AKR1C3; 4D label-free proteomics; castration-resistant prostate cancer; nucleic acid nanoparticles; PAMAM (G5) dendrimers
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2022.1069033

AKR1C3, as a crucial androgenic enzyme, implicates the androgen biosynthesis and promoting prostate cancer cell growth . This study provides a new gene therapy strategy for targeting AKR1C3 to treat castration-resistant prostate cancer. siAKR1C3@PPA is assembled from PEG3500, PAMAM, Aptamer-PSMA, and siRNA for AKR1C3. We analyzed the relationship between AKR1C3 expression and the survival rate of prostate cancer patients based on the GEPIA online database to perform disease-free survival, and found that AKR1C3 may be an important factor leading to poor prognosis in prostate cancer. Considering AKR1C3 as a therapeutic target for castration-resistant prostate cancer, we constructed a complex nucleic acid nanoparticle, siAKR1C3@PPA to investigate the inhibitory effect on castration-resistant prostate cancer. Aptamer-PSMA acts as a target to guide siAKR1C3@PPA into PSMA-positive prostate cancer cells and specifically down regulate AKR1C3. Cyclin D1 was decreased as a result of siAKR1C3@PPA treatment. Changes in Cyclin D1 were consistent with decreased expression of AKR1C3 in LNCaP-AKR1C3 cells and 22RV1 cells. Furthermore, in the LNCaP-AKR1C3 group, 1070 proteins were upregulated and 1015 proteins were downregulated compared to the LNCaP group according to quantitative 4D label-free proteomics. We found 42 proteins involved in cell cycle regulation. In a validated experiment, we demonstrated that PCNP and CINP were up-regulated, and TERF2 and TP53 were down-regulated by western blotting. We concluded that siAKR1C3@PPA may arrest the cell cycle and affect cell proliferation.