De Marco Margot, Falco Antonia, Festa Michela, Raffone Antonio, Sandullo Lucia, Rosati Alessandra, Reppucci Francesca, Cammarota Anna Lisa, Esposito Franca, Matassa Danilo Swann, Pascale Maria, Salzano Francesco, Martinelli Rosanna, Remondelli Paolo, Capunzo Mario, Mollo Antonio, Zullo Fulvio, Travaglino Antonio, Guida Maurizio, Marzullo Liberato
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno 84081 Baronissi, Italy.
Department of Pharmacy, University of Salerno 84084 Fisciano, Italy.
Am J Cancer Res. 2020 Aug 1;10(8):2596-2602. eCollection 2020.
Interleukin (IL)-6 has been detected in serum and ascites from patients affected by epithelial ovarian cancers, and also in some human ovarian cancer cell lines. To investigate the role of IL-6 in ovarian lesions, we first measured its levels in serum samples of 24 healthy donors and in 17 and 9 patients affected by ovarian carcinomas and ovarian benign cysts respectively. IL-6 levels were significantly higher than healthy donors in serum samples from ovarian cancer patients, but not in benign ovarian cysts. We then investigated the mechanism of IL-6 production in two cell lines obtained from the same patient with high grade serous ovarian carcinoma before (PEA1) and after (PEA2) development of cisplatinum resistance. The levels of intracellular IL-6, analysed by western blotting, did not relevantly differ in the two cell lines, and they did not change after the cell treatment with an AKT inhibitor. Although the interleukin was present in supernatants from both cell lines, its concentration in the supernatant of chemoresistant cells was significantly higher than chemosensitive cells. Interestingly, exposure to the AKT inhibitor resulted in a reduced IL-6 release in PEA1, but not in PEA2 cells. These results let infer different mechanisms of IL-6 release in chemoresistant and chemosensitive cell lines, and contribute new insights in ovarian cancer biology that suggest more in depth studies about the role of AKT in IL-6 release and in development of chemoresistance.
在上皮性卵巢癌患者的血清和腹水中以及一些人卵巢癌细胞系中均检测到白细胞介素（IL）-6。为了研究IL-6在卵巢病变中的作用，我们首先检测了24名健康供体以及分别患有卵巢癌和卵巢良性囊肿的17名和9名患者血清样本中的IL-6水平。卵巢癌患者血清样本中的IL-6水平显著高于健康供体，但卵巢良性囊肿患者血清中的IL-6水平则不然。然后，我们研究了从同一例高级别浆液性卵巢癌患者在顺铂耐药发生前（PEA1）和发生后（PEA2）获得的两个细胞系中IL-6的产生机制。通过蛋白质印迹分析的细胞内IL-6水平在这两个细胞系中没有显著差异，并且在用AKT抑制剂处理细胞后也没有变化。尽管两个细胞系的上清液中都存在白细胞介素，但其在化疗耐药细胞上清液中的浓度显著高于化疗敏感细胞。有趣的是，暴露于AKT抑制剂会导致PEA1细胞中IL-6释放减少，但PEA2细胞中则不然。这些结果提示了化疗耐药和化疗敏感细胞系中IL-6释放的不同机制，并为卵巢癌生物学提供了新的见解，表明需要更深入地研究AKT在IL-6释放和化疗耐药发展中的作用。
