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.

糖生物碱已被广泛证明是潜在的抗癌剂。然而，尚未探索这些化合物与传统化疗药物的化学增敏作用。为了寻求治疗膀胱癌 (BC) 的新型有效疗法，我们使用 2D 和 3D 细胞培养模型评估了配糖生物碱提取物 (GE) 与顺铂 (cDDP) 在 RT4 和 PDX 细胞中的化学增敏潜力。此外，我们还研究了 RT4 细胞中这种效应背后的潜在分子机制。在此，我们观察到与 RT4 细胞相比，PDX 细胞对顺铂具有高度抗性。集成电路₅₀与 RT4 细胞和 PDX 细胞中的 2D 单层相比，3D 培养物中的值分别显示出至少 2.16 倍和 1.4 倍。GE + cDDP 在 RT4 细胞中抑制集落形成 (40%) 和迁移 (28.38%) 并诱导细胞凋亡 (57%)。联合治疗通过下调 Bcl-2 ( p  < 0.001)、Bcl-xL ( p  < 0.001) 和存活 蛋白( p < 0.01) 的表达并激活 RT4 细胞中的半胱天冬酶级联反应来诱导细胞凋亡。此外，MMP-2 和 9 的表达降低（p < 0.01) 在联合治疗中观察到，暗示其对细胞侵袭/迁移的影响。此外，我们使用 3D 生物打印技术使用海藻酸钠-明胶作为生物墨水来生长 RT4 球体，并评估了 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。总之，我们展示了 GE 对 BC 细胞的细胞毒性作用，并且还证明了 GE 可以使 BC 细胞对化疗敏感。