The inhibitory effect of Licochalcone B on the triple negative breast cancer cell MDA-MB-231 and its mechanism / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨甘草查尔酮B（LCB）对三阴性乳腺癌（TNBC）MDA-MB-231细胞的抑制作用及其机制。方法: 常规培养MDA-MB-231细胞，用不同浓度LCB处理后，采用CCK-8法、免疫荧光法、FCM和WB法分别检测MDA-MB-231细胞的增殖活力、细胞核内DNA双链断裂标志物γ-H2AX的表达，以及细胞周期和周期调控、丝裂原活化蛋白激酶（MAPK）、内质网应激信号途径相关蛋白的表达水平。结果: LCB能显著抑制乳腺癌MDA-MB-231细胞的增殖活力（P<0.05），使γ-H2AX阳性细胞数和蛋白表达水平均显著升高（均P<0.05）、G2/M和S期的细胞数量均明显增加（均P<0.05）、MAPK家族主要成员细胞外调节激酶1/2（ERK1/2）和p38MAPK蛋白的磷酸化水平均显著上调（均P<0.05），还使内质网应激途径相关蛋白Bip、ATF4和CHOP的表达均显著上调（均P<0.05）。结论: LCB能够显著抑制MDA-MB-231细胞的增殖活力、诱导DNA损伤和细胞周期阻滞于G2/M和S期，LCB对MDA-MB-231细胞的抑制作用可能与其激活MAPK和内质网应激信号通路相关。

Bromodomain containing protein represses the Ras/Raf/MEK/ERK pathway to attenuate human hepatoma cell proliferation during HCV infection.

Hepatitis C virus (HCV) infection facilitates the development of hepatocellular carcinoma (HCC). Activation of Ras/Raf/MEK/ERK pathway is found in more than 30% human cancers. Here, we revealed a novel mechanism underlying the regulation of hepatoma cell proliferation mediated by HCV. On one hand, hepatoma cell proliferation is facilitated by HCV infection through a positive feedback regulatory cycle. HCV promotes hepatoma cell proliferation by activating the Ras/Raf/MEK/ERK pathway, which in turn facilitates HCV replication to further enhance hepatoma cell proliferation. On the other hand, hepatoma cell proliferation is attenuated by the bromodomain containing 7 (BRD7), a tumor suppressor, through a negative feedback regulatory mechanism. After activation, the Ras/Raf/MEK/ERK pathway stimulates BRD7 production, which in turn represses the Ras/Raf/MEK/ERK pathway, leading to the attenuation of hepatoma cell proliferation. However, HCV persistent infection attenuates BRD7 gene expression and facilitates the protein degradation to release the Ras/Raf/MEK/ERK signaling, which results in the facilitation of hepatoma cell proliferation. Therefore, we proposed that the balance between BRD7 function and Ras/Raf/MEK/ERK activity is important for determining the outcomes of HCV infection and HCC development.

Hepatitis B virus hijacks CTHRC1 to evade host immunity and maintain replication.

Hepatitis B virus (HBV) infection causes acute and chronic liver diseases, but is not directly cytopathic. Liver injury results from repeated attempts of the cellular immune response system to control the viral infection. Here, we investigate the roles of cellular factors and signaling pathways involved in the regulation of HBV replication to reveal the mechanism underlying HBV infection and pathogenesis. We show that collagen triple helix repeat containing 1 (CTHRC1) expression is elevated in HBV-infected patients and in HBV-transfected cells through epigenetic modification and transcriptional regulation. CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activating the PKCα/ERK/JNK/c-Jun cascade to repress the IFN/JAK/STAT pathway. HBV-activated CTHRC1 downregulates the activity of type I interferon (IFN), the production of IFN-stimulated genes (ISGs), and the phosphorylation of signal transducer and activator of transcription 1/2 (STAT1/2), whereas it upregulates the phosphorylation and ubiquitination of type I IFN receptors (IFNARα/ß). Thus, our results show that HBV uses a novel mechanism to hijack cellular factors and signal cascades in order to evade host antiviral immunity and maintain persistent infection. We also demonstrate that CTHRC1 has a novel role in viral infection.

Electrochemically deposited nanocomposite of chitosan and carbon nanotubes for detection of human chorionic gonadotrophin.

A new label-free amperometric immunosensor was developed for detection of human chorionic gonadotrophin (hCG) based on multiwall carbon nanotubes-chitosan (MWNTs-CS) complex film and three-dimensional AuNPs-TiO(2) hybrid. Firstly, MWNTs-CS film was deposited on a glassy carbon electrode (GCE) by a simple and controllable electrodeposition method. Next, thionine (Thi), as a redox probe, was covalently bound onto the MWNTs-CS film with glutaraldehyde (GA) to obtain the Thi/MWNTs-CS film. The free amino groups of the composite membrane were used to adsorb AuNPs-TiO(2) for immobilizing human chorionic gonadotrophin antibody (anti-hCG) because of its large surface area and satisfactory biocompatibility. At last, BSA was employed to block possible remaining active sites. Under optimized conditions, the immunosensor displayed high sensitivity, good reproducibility, and a low detection limit of 0.08mIU/mL at 3 times the background noise. The ease of non-manual technique and the promising feature of biocomposite could serve as a versatile platform for constructing other biosensors.