Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines
Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines
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DOI：
10.3390/curroncol29060321
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发表时间：
2022-06-01
期刊：
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
--
作者：
很少有研究报道激素制剂用于治疗低级别浆液性卵巢癌（LGSOCs），这是化疗耐药。考虑到需要新的有效治疗方法，我们研究了lgsoc中激素受体的表达和激素抑制效果。应用免疫组化技术，我们评估了33例组织学证实的浆液性卵巢肿瘤中雌激素受体（ER）的表达情况，其中分别包括10例、11例和12例lgsoc、浆液性交界性肿瘤（sbt）和浆液性囊腺瘤（SCAs）。本研究采用我们之前研究中报道的遗传背景。从lgsoc中培养的MPSC1细胞用于细胞增殖试验。我们观察到，ER在lgsoc和SBTs中的表达高于SCAs（分别为70%、81%和50%）。因此，lgsoc和SBTs比sca表达更高的ER。此外，PIK3CA突变与lgsoc中ER表达呈正相关（p = 0.0113）。Western blot显示MPSC1细胞ER表达较低。氟维司汀（选择性内质网下调剂）显著抑制MPSC1细胞增殖。ER和PI3K/AKT信号通路的激活可能在LGSOC癌变中发挥重要作用。氟维司汀下调内质网或与PI3K抑制剂联合治疗可能是lgsoc患者的一种新治疗方法。
Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.
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激素治疗用于治疗复发性低级别浆液性卵巢癌或腹膜癌。
影响因子：
4.7
作者：
Gershenson DM;Sun CC;Iyer RB;Malpica AL;Kavanagh JJ;Bodurka DC;Schmeler K;Deavers M
通讯作者：
Deavers M
影响因子：
3.9
作者：
Chen, S;Zhou, D;Yang, C
通讯作者：
Yang, C
影响因子：
--
作者：
Ciucci A;Zannoni GF;Buttarelli M;Lisi L;Travaglia D;Martinelli E;Scambia G;Gallo D
通讯作者：
Gallo D
影响因子：
4.7
作者：
Fader, Amanda Nickles;Java, James;Gershenson, David M.
通讯作者：
Gershenson, David M.
影响因子：
7.2
作者：
Gershenson, David M.;Sun, Charlotte C.;Bodurka, Diane C.
通讯作者：
Bodurka, Diane C.