Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a hydroxycinnamic acid derived from a rich polyphenolic compound. This study aimed to investigate the effect of ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA) on cell proliferation, invasion, apoptosis, and autophagy in Hela and Caski cervical carcinoma cell lines. The cell proliferation of FA in Hela and Caski cells were detected by MTT assay. The cell invasion of FA in Hela and Caski cells were detected by Transwell assay. Subsequently, MMP-9 mRNA expression for cell invasion was detected by RT-PCR. Additionally, cell cycle and apoptosis were assayed using flow cytometry. Expression levels of 7 proteins for both cell cycle and autophagy were measured by Western blot analysis. After treated with FA (2.0 mM) for 48 h, the inhibition rates of FA in Hela and Caski cells were 88.3 and 85.4%, respectively. In addition, FA inhibited cell invasion through reducing MMP-9 mRNA expression. FA induced arrest in G0/G1 phase of the cell cycle in Hela and Caski cells with dose dependent (P < 0.05). Meanwhile, FA induced the cell cycle-related proteins expression such as p53 and p21, and reduced Cyclin D1 and Cyclin E levels. Moreover, FA decreased the autophagy-related proteins such as LC3-II, Beclin1 and Atg12-Atg5 in a dose-dependent manner. FA can significantly inhibit cell proliferation and invasion in Hela and Caski cells. It might be acted as an anti-cancer drug through inhibiting the autophagy and inducing cell cycle arrest in human cervical carcinoma cells.

Background: To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. Methods: Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). Results: In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. Conclusions: IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow.

Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS’s anti-CC effects, and SS’s inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca²⁺ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.

Integrin-linked kinase (ILK) plays a role in the regulation of multiple cellular functions (e.g., promoting cell migration and proliferation, but inhibiting cell adhesion). This study investigated the inhibitory effects of ILK gene knockdown on the regulation of in vivo tumorigenesis of human ovarian carcinoma cells in nude mouse xenografts. HO-8910 cells were transfected with an ILK antisense oligonucleotide (ILK-ASO) to silence the ILK gene. Expression of ILK mRNA and protein was evaluated by RT-PCR and western blotting, respectively. The cell cycle was assessed by flow cytometric analysis. Cells with or without ILK-ASO transfection were subcutaneously injected into nude mice. The mouse body weight, tumor formation, tumor size and tumor weight were determined up to 30 days after inoculation. Tumor cells transfected with ILK-ASO had significantly decreased ILK mRNA and protein expression (P<0.01) when compared to the control cells. ILK gene silencing significantly increased the number of cells in the G0/G1 phase (67.61 vs. 43.29%, χ2=1197.15, P<0.01). After tumor cell inoculation, tumor cells transfected with ILK-ASO showed significantly delayed tumor formation when compared to control (9.10±0.74 vs. 5.30±0.67 days, respectively; P<0.01). In addition, tumor growth was suppressed in the 30 days following inoculation (P<0.01 compared with the controls). The average tumor weight in the ILK-ASO group was statistically lower than that of the control group (1.29±0.11 vs. 1.57±0.13 g, respectively; P<0.01). This study demonstrated that ILK-ASO transfection efficiently downregulated ILK expression in human ovarian carcinoma HO-8910 cells and that ILK gene silencing suppressed tumor growth in nude mice xenografts.

Cervical cancer is the second most common female malignancy worldwide. The metabolic profile of plasma associated with the prognosis of cervical cancer remains poorly understood. In this cross-sectional study, plasma samples were collected from three groups of patients with CSCC, namely primary patients before treatment (BT group), patients with a poor prognosis (PP group, including patients with distant metastasis and local recurrence), and patients with a good prognosis within two years after the first treatment (GP group). The plasma metabolomics was conducted to detect the dynamic changes of metabolites via ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Multivariate analyses, including principle component, partial least square-discriminant, and orthogonal projection to latent structure-discriminant analyses, were performed to compare each pair of the three groups. The differential metabolites were identified by comparison of the exact m/z values and mass spectrometry (MS)/MS spectra with the structural information of the metabolites obtained from the Human Metabolome Database (http://www.hmdb.ca/) and LIPID MAPS (http://www.lipidmaps.org/). To screen for potential markers, receiver operating characteristic curve analysis of the differential metabolites. Finally, thirty plasma samples were collected from each group. Multivariate analyses showed that 31 metabolites were significantly different among the 3 groups studied. Of those, the 5 metabolites phosphatidyl choline (15:0/16:0), phosphatidyl glycerol (12:0/13:0), actosylceramide (d18:1/16:0), D-Maltose, and phthalic acid, with an area under the curve above 0.75, were identified as potential biomarkers. The present findings provide evidence for biomarkers to monitor prognosis of patients with CSCC, which may help in better managing the disease.