Purpose: Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on human gastric carcinoma and underlying mechanism of action. Methods: Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway. Results: We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application. Conclusion: UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway.

2018-10-01·médecine/sciences4区 · 医学

UNBS5162 inhibits colon cancer growth via suppression of PI3K/Akt signaling pathway

4区 · 医学

Article

作者: Zhang, Fan ; Lv, Hui-Zeng ; Liu, Ji-Ming ; Ye, Xiao-Yong ; Wang, Cun-Chuan

Colon cancer is a common cause of cancer-related death worldwide. However, the underlying mechanism of tumor progression of colon cancer remains far from being elucidated. In the present study, we report the role of UNBS5162 in colon cancer. UNBS5162 is a naphthalimide that can intercalate into DNA and suppress the expression level of CXCL chemokines. Here, we investigated its effect on cell proliferation, mobility and apoptosis in HCT116 cells, and explored the underlying mechanism. A CCK8 assay revealed that UNBS5162 can block the proliferation of colon cancer cells. Base on a Transwell assay, we showed that cell migration and invasion ability of HCT116 cells are inhibited by UNBS5162. In addition, Annexin V-FITC/PI assay and Western blot analysis were performed to detect whether UNBS5162 could induce cell apoptosis. The results indicated that UNBS5162 increases the number of apoptotic cells remarkably. Furthermore, Western blot analysis demonstrated that UNBS5162 down-regulates the expression level of Bcl2, and up-regulates that of Bax as well as the level of activated Caspase-3. Moreover, we examined the impact of UNBS5162 on PI3K/Akt signaling pathway. UNBS5162 substantially inhibited the phosphorylation of Akt and its downstream effector mTOR, and reduced the expression of p-70. Taken together, these results suggest that UNBS5162 should be considered as a potent therapeutic anticancer agent that targets the PI3K/AKT signaling pathway.

2018-01-01·Thoracic Cancer3区 · 医学

UNBS5162 inhibits the proliferation of human A549 non‐small‐cell lung cancer cells by promoting apoptosis

3区 · 医学

ArticleOA

作者: Xing, Jiaqiang ; Gao, Yujun ; Liu, Cuicui

BackgroundLung cancer is one of the most frequently diagnosed malignancies in the world, thus developing novel anticancer reagents for lung cancer treatment is critical.MethodsWe performed cell counting kit‐8 and cell colony formation assays to investigate the role of UNBS5162 in the proliferation of A549 cells. Invasion and migration assays were applied to study the inhibitory effect of UNBS5162 on non‐small cell lung cancer cells. To detect the effect of UNBS5162 on A549 cell apoptosis, Annexin‐V fluorescein isothiocyanate and propidium iodide staining methods were used. Protein expression was analyzed using Western blot assay.ResultsUNBS5162 not only inhibited proliferation but also decreased invasion and migration in A549 cells. Most cells were intact (96.93%) under control conditions, but the number of intact cells decreased (84.8%) after 24 hours of treatment with UNBS5162, and the number of early and late apoptotic cells significantly increased (P < 0.05). Anti‐apoptotic protein Bcl‐2 expression in the UNBS5162 group was significantly decreased (P < 0.05), and expression of proapoptotic proteins Bim, Bax, and active caspase‐3 were significantly increased (P < 0.05) compared to the control. In the PI3K signaling pathway, phospo‐AKT and phospo‐mTOR levels were significantly decreased (P < 0.05), while S6K and Cyclin D1 protein levels were significantly decreased in UNBS5162 treated A549 cells (P < 0.05).ConclusionThese findings suggest that UNBS5162 could inhibit A549 cell proliferation and metastasis by inhibiting PI3K pathway mediated apoptosis.

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