Glioblastomas are the most aggressive type of brain tumour, with poor prognosis even after standard treatment such as surgical resection, temozolomide and radiation therapy. The overexpression of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) in glioblastomas is recognized as an important treatment target. Thus, an urgent need regarding glioblastomas is the development of a new, suitable agent that may show potential for the inhibition of extracellular signal‐regulated kinase (ERK)/NF‐κB–mediated glioblastoma progression. Imipramine, a tricyclic antidepressant, has anti‐inflammatory actions against inflamed glial cells; additionally, imipramine can induce glioblastoma toxicity via the activation of autophagy. However, whether imipramine can suppress glioblastoma progression via the induction of apoptosis and blockage of ERK/NF‐κB signalling remains unclear. The main purpose of this study was to investigate the effects of imipramine on apoptotic signalling and ERK/NF‐κB–mediated glioblastoma progression by using cell proliferation (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide [MTT] assay), flow cytometry, Western blotting, and cell invasion/migration assay analysis in vitro. The ERK and NF‐κB inhibitory capacity of imipramine is detected by NF‐κB reporter gene assay and Western blotting. Additionally, a glioblastoma‐bearing animal model was used to validate the therapeutic efficacy and general toxicity of imipramine. Our results demonstrated that imipramine successfully triggered apoptosis through extrinsic/intrinsic pathways and suppressed the invasion/migration ability of glioblastoma cells. Furthermore, imipramine effectively suppressed glioblastoma progression in vivo via the inhibition of the ERK/NF‐κB pathway. In summary, imipramine is a potential anti‐glioblastoma drug which induces apoptosis and has the capacity to inhibit ERK/NF‐κB signalling.

Background/Aim: Amentoflavone, an effective compound derived from medicinal plants, has been shown to boost therapeutic efficacy of chemotherapy in non-small cell lung cancer (NSCLC). However, anti-NSCLC effect of amentoflavone is ambiguous. The major purpose of the present study was to verify the inhibitory effects of amentoflavone in NSCLC cells. Materials and Methods: The effects of amentoflavone on growth and invasion of NSCLC CL-1-5-F4 cells were evaluated by cell viability assay, flow cytometry, colony formation assay, nuclear factor-kappa B (NF-κB) reporter gene assay, immunofluorescence staining, transwell invasion, and western blot assay. Results: Amentoflavone effectively induced cell growth inhibition, G1 cell-cycle arrest, apoptosis, and suppression of invasion. Furthermore, amentoflavone not only triggered expression of p27, cleaved caspase-3, -8 also reduced NF-κB signaling, protein levels of matrix metalloproteinase (MMP)-2, -9, Cyclin-D1, and vascular endothelial growth factor (VEGF). Conclusion: Cell-cycle arrest, apoptosis induction, NF-κB signaling inhibition are associated with amentoflavone-inhibited growth and invasion of NSCLC cells.

Although sorafenib, an oral multikinase inhibitor, was approved as a treatment drug of advance hepatocellular carcinoma (HCC), treatment efficacy still requires improvement. Searching for the adjuvant reagent for enhancing sorafenib efficacy remains as a critical issue. Sorafenib has been proved to suppress extracellular signal-regulated kinases (ERK) in HCC; however, protein kinase B (AKT) was not affected by it. Targeting AKT in combination with sorafenib could be an important breakthrough point of HCC treatment. Many herbal compounds and composite formulas have been shown to enhance anti-HCC activity of sorafenib. Magnolol is a bioactive compound extracted from the bark of the Magnolia officinalis and has been shown to induce apoptosis and inhibit cell invasion in HCC in vitro. However, whether magnolol sensitizes HCC to sorafenib is ambiguous. In this study, we indicated that magnolol significantly enhanced sorafenib-diminished tumor cell growth, expression of anti-apoptotic proteins, and migration/invasion ability compared to sorafenib alone. Magnolol significantly boosted sorafenib-induced extrinsic/intrinsic dependent apoptosis pathways in HCC. Notably sorafenib could not reduce protein level of AKT (Ser473), but expression of AKT (Ser473) was significantly decreased by magnolol or magnolol combined with sorafenib. LY294002 as specific AKT inhibitor was used to confirm that AKT inactivation may promote anticancer effect of sorafenib. Taken together, AKT inhibition is associated with magnolol-enhanced the therapeutic effect of sorafenib in HCC. We suggested magnolol as the potential adjuvant which may enhance therapeutic benefits of sorafenib in patients with HCC.

Background/Aim: Hepatocellular carcinoma (HCC) is a primary liver cancer with limited treatment options and poor prognosis. Regorafenib, a multi-kinase inhibitor, has shown promise in HCC treatment; however, its efficacy can be enhanced by combining it with other agents. 18β-glycyrrhetinic acid (18β-gly) is a natural compound with potential anti-cancer properties. Materials and Methods: The toxicity and mechanism of regorafenib and 18β-gly was assessed on Hep3B cells, Huh7 cells, and Hep3B bearing animal model. Results: The combination of regorafenib and 18β-gly exhibited synergistic toxicity in HCC cells and animal model. Importantly, no significant differences in body weight or major tissue damage were observed after treatment with the combination of two drugs. Furthermore, the combination treatment modulated apoptosis-related markers and the mTOR signaling pathway. Conclusion: The study provides evidence for the synergistic effect of 18β-gly and regorafenib in a HCC model. The combination treatment modulated apoptosis-related markers and the mTOR signaling pathway, highlighting potential mechanisms underlying its therapeutic efficacy.

Radioliposomes have potential applications as theranostic nanoparticles. Several techniques have been developed to label liposomes with radionuclides. Methods: In this study, a new In-111 surface labeling method for 1,4,7,10-tetraazacyclododecane-N, N', N", N'"-tetraacetic acid (DOTA) derivative liposomes (DLs) is described. The in vitro stability and in vivo molecular imaging properties of the labeled liposomes were compared with those of conventional ¹¹¹ In-liposomes ( ¹¹¹ In-Ls) prepared by a remote loading method. In vitro stability tests were performed in normal saline, rat plasma, and human plasma at 37°C. Imaging characteristics of both radioliposomal preparations were determined in LS174T tumor-bearing mice. Results: The labeling efficiency of In-111-labeled DL ( ¹¹¹ In-DLs) was greater than 95%; accordingly, no post-labeling purification was required, in contrast to the ¹¹¹ In-Ls. The specificity of ¹¹¹ In-DLs was higher (>10 ¹¹¹ In per liposome) than that of ¹¹¹ In-Ls (<;2 ¹¹¹ In per liposome). The two radioliposomes showed similar in vitro stability. Non-invasive longitudinal monitoring by micro-single-photon emission computed tomography/computed tomography showed a similar in vivo tumor distribution for the two radioliposomes (48 h post-injection, P > 0.05). Conclusion: The new ¹¹¹ In surface labeling method for liposomes was rapid, efficient, highly specific activity, and easy to perform. Although the two radioliposomes showed similar in vitro and in vivo characteristics, ¹¹¹ In-DLs have benefits for clinical drug preparation, and this surface labeling method is a promising platform for radioliposomal theranostic nanoparticle preparation.