Tumor cell-derived microparticles (MP) can function as a targeted delivery carrier for anti-tumor drugs. Here, we aimed to generate paclitaxel-loaded microparticles (MP-PTX) from HeLa cells and examined its therapeutic potential on human cervical carcinoma. Methods: MP-PTX was generated from HeLa cells by ultraviolet radiation and subsequent centrifugation. The particle size, drug loading rate, and stability of MP-PTX were examined in vitro. Flow cytometry and the MTT assay were performed to test the inhibitory effect of MP-PTX using different cell lines. Immunodeficient mice bearing HeLa cervical carcinoma were treated with 0.9% normal saline, MP, paclitaxel (PTX) (2.5 mg/kg), or MP-PTX (PTX content identical to PTX group) every day for 6 consecutive days. Tumor volume and animal survival were observed. Micro 18 F-FDG PET/CT was performed to monitor the therapeutic efficacy. The proliferation activity of cells and microvessel density in tumor tissues were determined by immunohistochemical staining using Ki-67 and CD31, respectively. Results: Dynamic laser scattering measurements showed that the particle size of MP-PTX was 285.58 ± 2.95 nm and the polydispersity index was 0.104 ± 0.106. And the particle size of MP-PTX was not change at 4°C for at least one week. More than 1% of PTX in the medium could be successfully encapsulated into HeLa cell-derived MP. When compared with PTX, MP-PTX treatment significantly increased apoptosis of tumor cells and reduced their proliferation. In addition, MP-PTX showed lower toxicity to normal human umbilical vein endothelial cells (HUVEC) than PTX. In vivo studies further demonstrated that MP-PTX treatment significantly inhibited the growth of cervical carcinoma, prolonged the survival of tumor-bearing mice, and reduced the toxicity of PTX. Immunohistochemical staining revealed that MP-PTX treatment led to decreased Ki-67 positive tumor cells and decreased microvessel density in tumor tissues. Conclusion: Our results demonstrated that HeLa-derived MP-PTX significantly enhanced the anti-cancer effects of PTX with reduced toxicity, which may provide a novel strategy for the treatment of cervical carcinoma.

PurposeAutophagy, the process responsible for degrading cytoplasmic organelles to sustain cellular metabolism, has been associated with cancer initiation and progression. As TP53-induced glycolysis and apoptosis regulator (TIGAR) is among the important genes that can regulate autophagy, we aimed to investigate the correlation between the expression levels of TIGAR and the autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3B), as well as their association with clinical outcomes, in nasopharyngeal carcinoma (NPC) patients.MethodsWe detected the expressions of TIGAR and LC3B in 182 NPC tissue samples via immunohistochemical staining.ResultsA significant correlation between TIGAR and LC3B expressions was identified (P=0.045). Moreover, survival analysis showed that TIGAR− or LC3B+ expression was associated with improved overall survival, local regional failure-free survival, distant failure-free survival, and failure-free survival rates, compared with TIGAR+ or LC3B− expression, respectively. Meanwhile, when combining TIGAR with LC3B expression in terms of prognostic value, patients with TIGAR+/LC3B− expression were significantly disadvantaged with regard to overall survival, local regional failure-free survival, distant failure-free survival, and failure-free survival compared with other groups based on the log-rank test and Cox regression analyses (all P<0.05).ConclusionTIGAR and LC3B may be novel biomarkers for predicting the prognosis of NPC patients and could be utilized as potential targets for future therapeutics aimed at treating NPC patients.

Mitochondria have been described as ‘the powerhouse of the cell’ as the organelle generates the majority of adenosine triphosphate (ATP) in cells to support life. Mitochondria can be damaged due to stress, for example by reactive oxygen species (ROS). TP53-induced glycolysis and apoptosis regulator (TIGAR) serves a role in suppressing ROS damage and may protect mitochondria integrity. In the present study, the localization of TIGAR on mitochondria in 5–8F cells was demonstrated. Furthermore, it was indicated that the knockdown of TIGAR using lentivirus-short hairpin RNA induces the loss of mitochondrial membrane potential and cytochrome c leakage. However, these damaged mitochondria were not degraded in cells, but exhibited an abnormal appearance as indicated by mitochondrial swelling, crista collapse and vacuolization, with physiological dysfunction marked by reduced ATP production. Therefore, TIGAR maybe an indispensable protein for mitochondrial protection and degradation following cellular damage.

The present study was performed to determine the molecular mechanism of calcium gluconate (CG) in alleviating the toxic effect of hydrofluoric (HF) acid on human dermal fibroblasts (HDFs). HDF morphology was observed by optical microscopy and the vimentin immunofluorescence assay. Cell viability and apoptosis were evaluated by the Cell Counting Kit-8 and Annexin V/propidium iodide assays, respectively. The levels of apoptosis-associated factors, as well as Wnt2, Wnt3a and β-catenin were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. Levels of matrix metalloproteinase (MMP)-1 and basic fibroblast growth factor (bFGF) were detected by ELISA and western blotting. Carboxyterminal propeptide of type I collagen (CICP) was detected by ELISA, while L-Hydroxyproline (L-HYP) was detected by colorimetry. First, the morphology of normal HDFs was observed. Cell viability was inhibited and apoptosis was increased in a dose- and time-dependent manner following treatment with HF acid [0, 2, 4, 6, 8, 10 and 20% (v/v)] for 0, 2, 4, 6, 8, 10 and 20 min. The effects were blocked by CG at different doses (50, 100 and 200 µmol/l) and time points (6, 12 and 24 h), following treatment with 8% (v/v) HF acid for 6 min. The levels of Caspase-3, B-cell lymphoma (Bcl)-2 associated X protein, Wnt2, Wnt3a and β-catenin were decreased, whereas Bcl-2 was increased by CG treatment dose-dependently, when compared with HF control. CG promoted the expression of MMP-1, bFGF and L-HYP, and inhibited CICP, when compared with HF control. Based on the present results, CG alleviated the toxic effect of HF acid on HDFs by regulating the Wnt/β-catenin signaling pathway.