Abstract
Recent attention has focused on the development of an effective three-dimensional (3D) cell culture system enabling the rapid enrichment of cancer stem cells (CSCs) that are resistant to therapies and serving as a useful in vitro tumor model that accurately reflects in vivo behaviors of cancer cells. Presently, an effective 3D in vitro model of ovarian cancer (OC) was developed using a marine collagen-based hydrogel. Advantages of the model include simplicity, efficiency, bioactivity, and low cost. Remarkably, OC cells grown in this hydrogel exhibited biochemical and physiological features, including (1) enhanced cell proliferation, migration and invasion, colony formation, and chemoresistance; (2) suppressed apoptosis with altered expression levels of apoptosis-regulating molecules; (3) upregulated expression of crucial multidrug resistance-related genes; (4) accentuated expression of key molecules associated with malignant progression, such as epithelial–mesenchymal transition transcription factors, Notch, and pluripotency biomarkers; and (5) robust enrichment of ovarian CSCs. The findings indicate the potential of our 3D in vitro OC model as an in vitro research platform to study OC and ovarian CSC biology and to screen novel therapies targeting OC and ovarian CSCs.
Highlights
Ovarian cancer (OC) has the highest death rate among gynecologic cancers and is the fifth leading cause of cancer-related deaths in women, even though it ranks tenth in cancer incidence among women in the United States [1]
On day 10 of the culture, almost all spheroids from the three cell types were around 200 μm in diameter. This was comparable to a general spheroid-based drug screening size, suggesting that Marine collagen (MC)-B hydrogels provide a favorable milieu for the growth of ovarian cancer (OC) cell spheroids, which can be applied for the development of diagnostic and therapeutic strategies for OC
The findings indicated that the activation of the activation of the Bcl-2 family proteins (Bcl-2 and Bax), which are the key regulators of apoptosis, the Bcl-2 family proteins (Bcl-2 and Bax), which are the key regulators of apoptosis, is involved in the is involved in the molecular mechanism by which the 3D microenvironment in MC-B hydrogels molecular mechanism by which the 3D microenvironment in MC-B hydrogels regulates apoptosis in regulates apoptosis in OC cells
Summary
Ovarian cancer (OC) has the highest death rate among gynecologic cancers and is the fifth leading cause of cancer-related deaths in women, even though it ranks tenth in cancer incidence among women in the United States [1]. According to the American Cancer Society, an estimated 22,240 US were diagnosed as OC, and an estimated 14,070 died from OC in 2018 [2]. The high mortality rate of OC is due to its high incidence rate, diagnosis that is delayed until advanced stages, and the high rate of recurrence despite successful initial therapy [3]. Risk factors that might impact the diverse patterns and trends of OC incidence and mortality include low parity, oral contraceptive use, family history, old age, estrogen/hormone replacement therapy, and changes in diet and physical activity [4].
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