Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time

被引:4
作者
Bilbao, Michelle [1 ]
Katz, Chelsea [2 ]
Kass, Stephanie L. [2 ]
Smith, Devon [3 ]
Hunter, Krystal [3 ]
Warshal, David [4 ]
Aikins, James K. [5 ]
Ostrovsky, Olga [6 ]
机构
[1] Virtua Hlth, Virtua Gynecol Oncol, Voorhees, NJ 08043 USA
[2] Cooper Univ Hlth Care, Dept Obstet & Gynecol, Camden, NJ 08103 USA
[3] Cooper Univ Hlth Care, Div Urogynecol, Dept Obstet & Gynecol, Camden, NJ 08103 USA
[4] Cooper Univ Hlth Care, Cooper Res Inst, Dept Stat, Camden, NJ 08103 USA
[5] Cooper Univ Hlth Care, MD Anderson Canc Ctr Cooper, Dept Gynecol Oncol, Camden, NJ 08103 USA
[6] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA
关键词
high-grade serous ovarian cancer; recurrent ovarian cancer; chemoresistance; platinum resistance; taxane resistance; spheroids; organoids; classic chemotherapy; epigenetic therapy; panobinostat; PLATINUM-RESISTANT OVARIAN; EPITHELIAL OVARIAN; FALLOPIAN-TUBE; PHASE-II; RECURRENT; CARCINOMA; CISPLATIN; MICROENVIRONMENT; VORINOSTAT; EXPRESSION;
D O I
10.3390/biom11111711
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients' lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.
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页数:24
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