Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells.
Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells.
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使用 RT4 和患者来源的异种移植膀胱癌细胞的 2D 和 3D 模型中配糖生物碱提取物的细胞毒性和化学增敏作用。
DOI：
10.1016/j.msec.2020.111460
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Singh M
中科院分区：
文献类型：
--
作者：
Miranda MA;Marcato PD;Mondal A;Chowdhury N;Gebeyehu A;Surapaneni SK;Bentley MVLB;Amaral R;Pan CX;Singh M
糖苷生物碱已被广泛证明是潜在的抗癌药物。然而，这些化合物与传统化疗药物的化疗增敏作用尚未被探索。在寻求治疗膀胱癌（BC）的新的有效疗法的过程中，我们使用2D和3D细胞培养模型在RT 4和PDX细胞中评估了甘草提取物（GE）与顺铂（cDDP）的化学增敏潜力。此外，我们还研究了RT 4细胞中这种效应背后的潜在分子机制。在此，我们观察到PDX细胞与RT 4细胞相比对顺铂具有高度抗性。与RT 4细胞和PDX细胞中的2D单层相比，3D培养物中的IC 50值分别高出至少2.16倍和1.4倍。GE + cDDP可抑制RT 4细胞集落形成（40%）和迁移（28.38%），诱导细胞凋亡（57%）。联合治疗通过下调Bcl-2（p < 0.001）、Bcl-xL（p < 0.001）和Survivin（p < 0.01）的表达并激活RT 4细胞中的caspase级联反应来诱导凋亡。此外，观察到联合治疗降低MMP-2和MMP-9的表达（p < 0.01），暗示其对细胞侵袭/迁移的影响。此外，我们使用海藻酸钠-明胶作为生物墨水使用3D生物打印来生长RT 4球状体，并评估GE + cDDP对该系统的影响。细胞活力测定显示GE与cDDP对生物打印球体的化学增敏作用。综上所述，我们显示了GE对BC细胞的细胞毒性作用，也证明了GE可以使BC细胞对化疗敏感。
Glycoalkaloids have been widely demonstrated as potential anticancer agents. However, the chemosensitizing effect of these compounds with traditional chemotherapeutic agents has not been explored yet. In a quest for novel effective therapies to treat bladder cancer (BC), we evaluated the chemosensitizing potential of glycoalkaloidic extract (GE) with cisplatin (cDDP) in RT4 and PDX cells using 2D and 3D cell culture models. Additionally, we also investigated the underlying molecular mechanism behind this effect in RT4 cells. Herein, we observed that PDX cells were highly resistant to cisplatin when compared to RT4 cells. IC50 values showed at least 2.16-folds and 1.4-folds higher in 3D cultures when compared to 2D monolayers in RT4 cells and PDX cells, respectively. GE + cDDP inhibited colony formation (40%) and migration (28.38%) and induced apoptosis (57%) in RT4 cells. Combination therapy induced apoptosis by down-regulating the expression of Bcl-2 (p < 0.001), Bcl-xL (p < 0.001) and survivin (p < 0.01), and activating the caspase cascade in RT4 cells. Moreover, decreased expression of MMP-2 and 9 (p < 0.01) were observed with combination therapy, implying its effect on cell invasion/migration. Furthermore, we used 3D bioprinting to grow RT4 spheroids using sodium alginate-gelatin as a bioink and evaluated the effect of GE + cDDP on this system. Cell viability assay showed the chemosensitizing effect of GE with cDDP on bio-printed spheroids. In summary, we showed the cytotoxicity effect of GE on BC cells and also demonstrated that GE could sensitize BC cells to chemotherapy.
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影响因子：
3.4
作者：
Davarpanah NN;Yuno A;Trepel JB;Apolo AB
通讯作者：
Apolo AB
影响因子：
5.4
作者：
Jiang, Guoqiang;Liu, Jia;Li, Weiling
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影响因子：
5.4
作者：
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影响因子：
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作者：
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通讯作者：
Adham SA
DOI：
10.1016/j.bbrc.2016.05.161
发表时间：
2016-08-05
影响因子：
3.1
作者：
Hu, Jin;Xu, Minglong;Xu, Yinxue
通讯作者：
Xu, Yinxue