1.
Synergistic therapy of chemotherapeutic drugs and MTH1 inhibitors using a pH-sensitive polymeric delivery system for oral squamous cell carcinoma.
Li, X, Li, L, Huang, Y, Liu, B, Chi, H, Shi, L, Zhang, W, Li, G, Niu, Y, Zhu, X
Biomaterials science. 2017;(10):2068-2078
Abstract
MutT homolog 1 (MTH1) is an essential sanitizer of the free nucleotide pool that prevents lethal DNA damage in cancer cells, which has been validated as an anticancer target in recent years. Small molecule TH287 potently and selectively inhibits the MTH1 protein in cells. Here, we developed an effective chemotherapeutic system for oral squamous cell carcinoma (OSCC) based on polymeric nanoparticles that achieve co-delivery of anticancer drug sodium arsenite (NaAsO2) and MTH1 inhibitor TH287. Cationic hyperbranched poly(amine-ester) (HPAE), an amphiphilic and pH-sensitive polymer with a highly branched structure, self-assembled into nanoparticles in aqueous solution. Both NaAsO2 and TH287 could be loaded into HPAE nanoparticles with the help of electrostatic attraction and hydrophobic interaction. The release of NaAsO2 and TH287 from HPAE(NaAsO2 + TH287) nanoparticles was pH-dependent. In vitro evaluation demonstrated that the HPAE(NaAsO2 + TH287) nanoparticles rapidly entered cancer cells and released NaAsO2 and TH287 in response to acidic intracellular environments. In comparison with NaAsO2, TH287, HPAE(NaAsO2) nanoparticles, HPAE(TH287) nanoparticles, and the physical mixture of HPAE(NaAsO2) nanoparticles and TH287, the HPAE(NaAsO2 + TH287) nanoparticles exhibited more effective inhibition of tumor cell proliferation, illustrating the synergistic effect of NaAsO2 and TH287. The experimental results show that TH287 is likely to inhibit MTH1 in tumor cells, rendering them more sensitive to NaAsO2.
2.
Association of X-ray repair cross-complementing group 1 Arg194Trp, Arg399Gln and Arg280His polymorphisms with head and neck cancer susceptibility: a meta-analysis.
Wu, W, Liu, L, Yin, Z, Guan, P, Li, X, Zhou, B
PloS one. 2014;(1):e86798
Abstract
BACKGROUND Previous studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk. METHODS The PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals. RESULTS No significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models. CONCLUSION The meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.
3.
[Promoting effect of all-trans retinoic acid on the chemosensitivity of esophageal cancer EC9706 cells].
Lu, TY, Li, X, Li, WB, Wang, LX, Gao, DL, Wang, RL, Lu, SX, Fan, QX
Zhonghua zhong liu za zhi [Chinese journal of oncology]. 2010;(9):663-6
Abstract
OBJECTIVE To investigate the impact of all-trans retinoic acid (ATRA) on chemosensitivity to esophageal squamous cell carcinoma EC9706 cells in vitro and its mechanism. METHODS EC9706 cells were routinely cultured as the control group. The experimental group was divided into three groups. The ATRA group with ATRA in final concentration of 1 µmol/L; the 5-Fu group with 5-Fu in final concentration of 50 mg/L; the combined treatment group with ATRA in final concentration of 1 µmol/L and 5-Fu 50 mg/L. The cell apoptosis was detected by terminal deoxynucleotidy transferase mediated dUTP nick end labelling (TUNEL). The cell cycle and apoptosis were detected by flow cytometry. RESULTS The results of TUNEL showed that in the combined treatment group appeared a large number of apoptotic cells, and their nuclei were stained brown, with a positive rate of 89.7%. There was a significant difference in the comparison with the ATRA group (38.3%) and 5-Fu group (40.3%) (P < 0.05). The flow cytometry showed that the ATRA + 5-Fu group had a significantly higher apoptosis rate (76.9% ± 2.7%) than that in the ATRA group (38.2% ± 2.6%) and 5-Fu group (45.2% ± 2.3%) (P < 0.05). The ratio of cells in G(1) phase increased in the ATRA + 5-Fu group (83.4% ± 3.0%), significantly higher than (48.2% ± 2.5%) in the ATRA group and (53.2% ± 2.6%) in the 5-Fu group (P < 0.05). The ratio of cells in S + G(2)/M phase was decreased in the ATRA + 5-Fu group, with a significant difference (P < 0.05) when compared with other groups. There was no significant difference between the ATRA group and 5-Fu group (P > 0.05) in the apoptosis rate and the proportion of cells at different phases. CONCLUSION ATRA can induce apoptosis of esophageal carcinoma EC9706 cells in vitro. The combination of ATRA and 5-Fu may enhance the chemotherapeutic efficacy.