MiR-125b Inhibits Tumor Growth and Promotes Apoptosis of Cervical Cancer Cells by Targeting Phosphoinositide 3-Kinase Catalytic Subunit Delta

Background/Aims: Cervical cancer, which is one of the most aggressive cancers affecting females, has high rates of recurrence and mortality. Small nucleolar RNA host gene 12 (SNHG12) is known to promote the progression of several cancers; however, its exact effects and molecular mechanisms in cervical cancer remain unknown. Methods: Real-time quantitative PCR was used to determine the expression level of SNHG12 in cervical cancer tissues and cell lines. Loss-of-function assays were performed to examine the effect of SNHG12 on the proliferation, apoptosis, migration and invasion of cervical cancer cells in vitro and tumor growth in vivo. Luciferase experiments were employed to explore the interactions between SNHG12 and miR-424-5p. Results: SNHG12 was found to be abnormally elevated in human cervical cancer tissues compared with paired adjacent normal tissues. Moreover, high SNHG12 expression in tumor tissues was significantly correlated with vascular involvement, lymph node metastasis, advanced FIGO stage and poor prognosis. Furthermore, the knockdown of SNHG12 was found to inhibit proliferation, migration and invasion of cervical cancer cells in vitro, and silencing SNHG12 was shown to suppress tumor growth in a nude mouse model. Mechanistic studies showed that SNHG12 functioned as an endogenous sponge for miR-424-5p, thereby downregulating the expression of miR-424-5p in cervical cancer. Furthermore, the inhibition of miR-424-5p in SNHG12-depleted cells partially reversed the effects on cervical cancer cell apoptosis, adhesion and invasion. Conclusion: In summary, our findings suggest that the tumor-promoting role of SNHG12 is to function as a molecular sponge, which negatively regulates miR-424-5p. These findings may provide a potent therapeutic target for cervical cancer.

Download Full-text

Brucea javanica oil emulsion suppresses tumor growth in human cervical cancer cells through inhibition of the E6 oncogene and induction of apoptosis

Translational Cancer Research ◽

10.21037/tcr.2019.12.62 ◽

2020 ◽

Vol 9 (2) ◽

pp. 918-929

Author(s):

Ling Ye ◽

Jian-Fu Zhao ◽

Yi-Ming Wang ◽

Wen-Hui Chen ◽

Shen Qian ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Oil Emulsion ◽

Brucea Javanica ◽

Cervical Cancer Cells ◽

Induction Of Apoptosis ◽

Human Cervical Cancer Cells ◽

Brucea Javanica Oil ◽

Human Cervical Cancer

Download Full-text

VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway

Cancer Letters ◽

10.1016/j.canlet.2019.11.035 ◽

2020 ◽

Vol 470 ◽

pp. 64-74 ◽

Cited By ~ 1

Author(s):

Vivek K. Kashyap ◽

Nirnoy Dan ◽

Neeraj Chauhan ◽

Qinghui Wang ◽

Saini Setua ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Signaling Pathway ◽

P53 Signaling ◽

Cervical Cancer Cells ◽

P53 Signaling Pathway

Download Full-text

The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation

Cancers ◽

10.3390/cancers11121927 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1927 ◽

Cited By ~ 2

Author(s):

Joo Young Hong ◽

Kyung-Sook Chung ◽

Ji-Sun Shin ◽

Jeong-Hun Lee ◽

Hyo-Sun Gil ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cyclin D1 ◽

Cancer Cells ◽

Proliferative Activity ◽

Parp Cleavage ◽

Tunel Staining ◽

Cervical Cancer Cells ◽

Induction Of Apoptosis ◽

Human Cervical Cancer

We previously reported the potential anti-proliferative activity of 3-(5,6,7-trimethoxy-4-oxo-4H-chromen-2-yl)-N-(3,4,5-trimethoxyphenyl) benzamide (TMS-TMF-4f) against human cancer cells; however, the underlying molecular mechanisms have not been investigated. In the present study, TMS-TMF-4f showed the highest cytotoxicity in human cervical cancer cells (HeLa and CaSki) and low cytotoxicity in normal ovarian epithelial cells. Annexin V-FITC and propidium iodide (PI) double staining revealed that TMS-TMF-4f-induced cytotoxicity was caused by the induction of apoptosis in both HeLa and CaSki cervical cancer cells. The compound TMS-TMF-4f enhanced the activation of caspase-3, caspase-8, and caspase-9 and regulated Bcl-2 family proteins, which led to mitochondrial membrane potential (MMP) loss and resulted in the release of cytochrome c and Smac/DIABLO into the cytosol. Also, TMS-TMF-4f suppressed both constitutive and IL-6-inducible levels of phosphorylated STAT3 (p-STAT3) and associated proteins such as Mcl-1, cyclin D1, survivin, and c-Myc in both cervical cancer cells. STAT-3 overexpression completely ameliorated TMS-TMF-4f-induced apoptotic cell death and PARP cleavage. Docking analysis revealed that TMS-TMF-4f could bind to unphosphorylated STAT3 and inhibit its interconversion to the activated form. Notably, intraperitoneal administration of TMS-TMF-4f (5, 10, or 20 mg/kg) decreased tumor growth in a xenograft cervical cancer mouse model, demonstrated by the increase in TUNEL staining and PARP cleavage and the reduction in p-STAT3, Mcl-1, cyclin D1, survivin, and c-Myc expression levels in tumor tissues. Taken together, our results suggest that TMS-TMF-4f may potentially inhibit human cervical tumor growth through the induction of apoptosis via STAT3 suppression.

Download Full-text

Downregulation of microRNA‑1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin‑2

Oncology Letters ◽

10.3892/ol.2019.10571 ◽

2019 ◽

Cited By ~ 2

Author(s):

Ping Du ◽

Yue‑Hua Lai ◽

De‑Sheng Yao ◽

Jun‑Ying Chen ◽

Nan Ding

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cervical Cancer Cells

Download Full-text

Mechanistic basis of a combination d-penicillamine and platinum drugs synergistically inhibits tumor growth in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

Biochemical Pharmacology ◽

10.1016/j.bcp.2015.03.006 ◽

2015 ◽

Vol 95 (1) ◽

pp. 28-37 ◽

Cited By ~ 13

Author(s):

Szu-Jung Chen ◽

Ching-Chuan Kuo ◽

Hsin-Yi Pan ◽

Tsui-Chun Tsou ◽

Szu-Ching Yeh ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Platinum Drugs ◽

Cervical Cancer Cells ◽

Mechanistic Basis ◽

Human Cervical Cancer Cells ◽

Human Cervical Cancer

Download Full-text

Photodynamic Effects of Vitamin K3 on Cervical Carcinoma Cells Activating Mitochondrial Apoptosis Pathways

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200814164629 ◽

2020 ◽

Vol 21 (1) ◽

pp. 91-99

Author(s):

Yong Xin ◽

Wenwen Guo ◽

Chunsheng Yang ◽

Qian Huang ◽

Pei Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Caspase 3 ◽

Mitochondrial Apoptosis ◽

Caspase 9 ◽

Vitamin K3 ◽

Cervical Cancer Cells ◽

Apoptosis Pathways

Background: Photodynamic Therapy (PDT) is a photoactivation or photosensitization process, wherein vitamin K3 (Vit K3) serves as a photosensitizer to produce Reactive Oxygen Species (ROS) against bacteria at appropriate wavelengths. In this study, we used Vit K3 treatment combined with Ultraviolet radiation A (UVA) to produce photodynamic effects on cervical cancer. Methods: The dose-concentration relationship between Vit K3 treatment and UVA on tumor cells was analyzed through the Cell Counting Kit-8 method. Then, the morphological characteristics of apoptosis cells were observed through fluorescent staining and fluorescence microscopy. Apoptosis after treatment with Vit K3 treatment, UVA, and Vit K3 treatment plus UVA was further observed through Western blot analysis, flow cytometry, and TUNEL assay. The xenograft models from HeLa cells were established for the exploration of the photodynamic effect of Vit K3 treatment on cervical cancer in vivo. Results: Vit K3 treatment plus UVA reduced tumor cell viability in a dose-dependent manner. Further studies indicated that Vit K3 treatment plus UVA can inhibit tumor growth and enhance the apoptosis of cervical cancer cells. In the combination group, the expression levels of cleaved caspase-3, cleaved caspase-9, B-cell lymphoma- extra large (Bcl-xl), and cytochrome c (cyt-c) increased obviously, whereas the expression level of Bcell lymphoma 2 (Bcl-2) decreased relative to the expression levels of UVA- or Vit K3-treated cells. In the in vivo experiments, tumor growth was inhibited significantly in the VitK3 treatment plus UVA group. Additionally, we demonstrated that the combination therapy mediated an increase in cleaved caspase-3 and cleaved caspase-9 expression and decrease in Bcl-2 expression in vivo. Conclusion: Our results showed that Vit K3 treatment combined with UVA exerted photodynamic effects on cervical cancer cells by activating mitochondrial apoptosis pathways.

Download Full-text

AKIP1 promotes angiogenesis and tumor growth by upregulating CXC-chemokines in cervical cancer cells

Molecular and Cellular Biochemistry ◽

10.1007/s11010-018-3335-7 ◽

2018 ◽

Vol 448 (1-2) ◽

pp. 311-320 ◽

Cited By ~ 14

Author(s):

Wenying Zhang ◽

Qiongwei Wu ◽

Chao Wang ◽

Longtao Yang ◽

Ping Liu ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cervical Cancer Cells

Download Full-text

A combination of anti-PD-L1 mAb plus Lm-LLO-E6 vaccine to suppress tumor growth and metastasis in HPV-infected cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23175 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23175-e23175 ◽

Cited By ~ 1

Author(s):

Po Lin Lin ◽

Yun Yen ◽

Huei Lee

Keyword(s):

Lung Cancer ◽

Cervical Cancer ◽

Antitumor Activity ◽

Tumor Growth ◽

Cancer Cells ◽

Nude Mice ◽

E7 Oncoprotein ◽

Cervical Cancer Cells ◽

Tumor Growth And Metastasis ◽

Nsclc Patients

e23175 Background: PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy for certain non-small cell lung cancer (NSCLC) patients. Methods: PD-L1 and E6 oncoprotein expressions in lung tumors from 122 NSCLC patients were examined by immunohistochemistry and their prognostic value was evaluated by Kaplain-Meier and Cox regression analysis. HPV16-postive and negative TL-1 and TL-4 lung cancer and SiHa and C33A cervical cancer cells were used to test whether PD-L1 expression could be regulated by E6, not by E7 oncoprotein. Immune deficiency nude mice were used to test the possibility that combining anti-PD-L1 mAb with Lm-LLO-E6 vaccine could have a higher antitumor activity compared with anti-PD-L1 mAb or Lm-LLO-E6 vaccine alone. Results: Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD-L1 expression was responsible for E6-mediated colony formation and soft agar growth. Therefore, PD-L1 secreted from tumor cells may directly promote tumor progression, particularly in E6-positive tumors. A greater antitumor activity was obtained with anti-PD-L1 mAb+Lm-LLO-E6 vaccine than with anti-PD-L1 mAb or Lm-LLO-E6 alone in subcutaneous and metastatic tumors induced by TL-1 and SiHa cells. The longest survival time for nude mice was observed in the anti-PD-L1 mAb+Lm-LLO-E6 vaccine group. Conclusions: An anti-PD-L1 mAb+Lm-LLO-E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV-infected cells.

Download Full-text