Department of Urology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, P.R. China.
Department of Urology, Renji Hospital Affiliated to the Medical School of Shanghai Jiaotong University, Shanghai 200000, P.R. China.
Oncol Rep. 2017 Nov;38(5):3160-3166. doi: 10.3892/or.2017.5993. Epub 2017 Sep 25.
Malignant pheochromocytoma (PHEO) is diagnosed only when metastasis has occurred, making it less likely for patients to obtain the benefits of traditional chemotherapy. Anti-oncogene TP53 mutation has been detected in PHEO and is possibly related to disease progression. However, whether the upregulation of wild-type TP53 has antitumoral effects on PHEO remains completely unknown. In the present study, we used RNA activation (RNAa) technique to upregulate the expression of wild-type TP53 by transfecting synthetic dsP53‑285 into PHEO cell line PC12. We found that the upregulation of wild-type p53 blocked the transition of PC12 cells from the G0/G1 to the S phase, with induction of apoptosis. Additionally, the above-mentioned findings were attested in vivo. Most importantly, dsP53-285-induced antitumoral effects were reversible following co-transfection with siRNA that targeted p53 mRNA. Collectively, our results revealed that the upregulation of p53 and possibly other anti-oncogenes may provide a potential effective therapeutic strategy for PHEO.
恶性嗜铬细胞瘤 (PHEO) 只有在转移发生时才被诊断出来，这使得患者不太可能从传统化疗中获益。已经在 PHEO 中检测到抑癌基因 TP53 突变，并且可能与疾病进展有关。然而，野生型 TP53 的上调是否对 PHEO 具有抗肿瘤作用仍完全未知。在本研究中，我们使用 RNA 激活 (RNAa) 技术通过转染合成的 dsP53-285 将野生型 TP53 的表达上调至 PHEO 细胞系 PC12 中。我们发现，野生型 p53 的上调阻止了 PC12 细胞从 G0/G1 期向 S 期的过渡，并诱导了细胞凋亡。此外，上述发现也在体内得到了证实。最重要的是，用靶向 p53 mRNA 的 siRNA 共转染后，dsP53-285 诱导的抗肿瘤作用是可逆的。总之，我们的结果表明，p53 及其他抑癌基因的上调可能为 PHEO 提供一种潜在有效的治疗策略。
