Potential Role of GST-π in Lung Cancer Stem Cell Cisplatin Resistance.

BACKGROUND: Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST-π is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST-π in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST-π in stemness and cisplatin (DDP) resistance of LCSCs. Materials and methods. In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST-π protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST-π expression in LCSCs were analyzed following the interference with GST-π using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine. RESULTS: The results revealed that GST-π was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both P < 0.05). Regulating GST-π protein expression could alter DDP resistance of LCSCs by influencing ROS. CONCLUSION: These results suggested that GST-π may be important for LCSC drug resistance by downregulating ROS levels. These findings may contribute to the development of new adjuvant therapeutic strategies for lung cancer.

Influence of alternated drying and wetting on the characteristics of soil preferential flow formation in Honghe Arid Valley.

To clarify the effects of alternation of drying and wetting on the formation of soil preferential flow in arid valley, taking the wasteland in the arid valley of Honghe River as the research object, we analyzed the soil preferential flow characteristics before and after the simulation of drying and wetting alternation based on dyeing tracer method, water breakthrough curve, and image processing technology. The results showed that, under the simulated alternation of drying and wetting, the matrix flow occurred in the 0-10 cm soil layer, the dyeing depth reached 35 cm, the horizontal width of the preferred path was only 3-10 cm, and the dyeing area curve fluctuated little. Simulated alternation of drying and wetting led to significant increases in the steady effluent, macropores number, and macroporosity. In the 0-20 cm soil layer, the steady effluent after alternation of drying and wetting was about 0.27 cm3·s-1 higher than that non-alternation of drying and wetting, macropores number in dyeing area was about 1.4 times higher, and the macroporosity was 13.4% higher. The macropores number was positively correlated with stable flow rate. After simulated alternation of drying and wetting, the number of macropores from large to small was 0.6-0.8 mm＞0.8-1.0 mm＞1.0-1.5 mm＞1.5-2.0 mm＞2.0-3.7 mm, while under non-alternation of drying and wetting, it was 0.8-1.0 mm＞0.6-0.8 mm＞1.0-1.5 mm＞2.0-3.7 mm＞1.5-2.0 mm. The macropores number in each pore size range was significantly correlated with the dyeing area ratio. After simulated alternation of drying and wetting, the correlation increased, and the dominant factor affecting the occurrence of preferential flow changed from the macropores number in the pore size range of 1.5-2.0 mm to that of 0.8-1.0 mm. Therefore, the alternation of drying and wetting would affect the characteristics of macropores, which caused the soil to be more prone to preferential flow and with higher magnitude.

Peptide nucleic acids targeting mitochondria enhances sensitivity of lung cancer cells to chemotherapy.

Acquired resistance to chemotherapy is a major limitation for the successful treatment of lung cancer. Previously, we and others showed that formation of tumor spheres is associated with chemotherapy resistance in lung cancer cells, but the underlying mechanisms remained largely unknown. In the current study, we show that mitochondrial activity is significantly higher in A549 tumor spheres versus monolayer cells, establishing mitochondria as a putative target for antitumor therapy. To this end, we designed a peptide nucleic acids (PNAs) coupled with triphenylphosphonium (TPP) to target the displacement loop (D-loop) regulatory region of mitochondrial DNA (PNA-mito). Treatment with PNA-mito significantly disrupted mitochondrial gene expression, inhibited membrane potential and mitochondria fusion, resulting in proliferation inhibition and cell death. Consistently, in mouse xenograft models, PNA-mito could efficiently inhibit mitochondrial gene expression and block tumor growth. Treatment with a low dose of PNA-mito could significantly enhance the chemotoxicity of cisplatin (CDDP) in drug-resistant A549 tumor spheres. These results establish mitochondria-targeting PNAs as a novel strategy to enhance the accumulative therapeutic outcome of lung cancer.

The association between MMP-12 82 A/G polymorphism and susceptibility to various malignant tumors: a meta-analysis.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for degrading essentially all components of the extracellular matrix (ECM). Accumulating evidence suggests that MMPs might play a critical role in growth, invasion, and metastasis of malignant tumors. A single nucleotide polymorphism (SNP) in the promoter region of MMP-12, MMP-12 82 A/G (rs2276109), has been recognized to play a critical role in regulating the expression of MMP-12, however, its correlation with tumor susceptibility remains controversial. To address this issue, we performed meta-analysis to investigate the association MMP-12 82 A/G polymorphism and susceptibility of nine malignant tumors from 11 studies, including 6153 cancer patients and 6838 controls. Two reviewers independently screened studies for eligibility and extracted data for included studies. While overall no evident association between MMP-12 82 A/G and tumor susceptibility was observed, subgroup analysis revealed a specific role of G allele in increasing the susceptibility for epithelial ovarian carcinoma (EOC) using the allele model (fixed effects OR = 2.45, 95% CI = 1.46-4.10, P = 0.001) and the dominant model (fixed effects OR = 2.52, 95% CI = 1.49-4.24, P = 0.001). We thus suggest that G allele of MMP-12 82 A/G polymorphism is a genetic risk factor for EOC.

Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells.

There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.

NRSN2 promotes non-small cell lung cancer cell growth through PI3K/Akt/mTOR pathway.

Neurensin-2 (NRSN2), a small neural membrane protein which localized in small vesicles in neural cells. Recent report suggested that Neurensin-2 might play a suppressive role in tumor. While the biological functions and molecular mechanisms in cancer progression remain unknown. We retrieved Oncomine Database and found that NRSN2 is commonly highly expressed in non-small cell lung cancer (NSCLC). We examined the levels of NRSN2 in 18 pairs of NSCLC and adjacent tissues and found that NRSN2 was overexpressed in malignant tissues. Both loss and gain of function experiments in NSCLC cell lines suggest that NRSN2 promotes cell growth, but no effects in cell invasion. Further investigation show that NRSN2 could affect phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling. Taken together, our findings suggest that NRSN2 promotes non-small cell lung cancer cell growth through PI3K/Akt/mTOR pathway.

Evidence for inbreeding depression and pre-copulatory, but not post copulatory inbreeding avoidance in the cabbage beetle Colaphellus bowringi.

Inbreeding is known to have adverse effects on fitness-related traits in a range of insect species. A series of theoretical and experimental studies have suggested that polyandrous insects could avoid the cost of inbreeding via pre-copulatory mate choice and/or post-copulatory mechanisms. We looked for evidence of pre-copulatory inbreeding avoidance using female mate preference trials, in which females were given the choice of mating with either of two males, a sibling and a non-sibling. We also tested for evidence of post-copulatory inbreeding avoidance by conducting double mating experiments, in which four sibling females were mated with two males sequentially, either two siblings, two non-siblings or a sibling and a non-sibling in either order. We identified substantial inbreeding depression: offspring of females mated to full siblings had lower hatching success, slower development time from egg to adult, lower survival of larval and pupal stages, and lower adult body mass than the offspring of females mated to non-sibling males. We also found evidence of pre-copulatory inbreeding avoidance, as females preferred to mate with non-sibling males. However, we did not find any evidence of post-copulatory inbreeding avoidance: egg hatching success of females mating to both sibling and non-sibling males were consistent with sperm being used without bias in relation to mate relatedness. Our results suggest that this cabbage beetle has evolved a pre-copulatory mechanism to avoid matings between close relative, but that polyandry is apparently not an inbreeding avoidance mechanism in C. bowringi.

Comparison of sexual compatibility in crosses between the southern and northern populations of the cabbage beetle Colaphellus bowringi.

It is widely accepted that the genetic divergence and reproductive incompatibility between closely related species and/or populations is often viewed as an important step toward speciation. In this study, sexual compatibility in crosses between the southern XS population and the northern TA population of the polyandrous cabbage beetle Colaphellus bowringi was investigated by testing their mating preferences, mating latency, copulation duration, and reproductive performances of post-mating. In choice mating experiments, the percentages of matings were significantly higher in intra-population crosses than in inter-population crosses. Both isolation index (I) and index of pair sexual isolation (IPSI ) indicated partial mating incompatibility or assortative mating in crosses between the two different geographical populations. In single pair mating experiments, XS females in inter-population crosses mated significantly later and copulated significantly shorter than those in intra-population crosses. However, TA females in inter-population crosses mated significantly earlier and copulated longer than those in intra-population crosses, suggesting that larger XS males may enhance heterotypic mating. The lifetime fecundity was highest in XS homotypic matings, lowest in TA homotypic matings, and intermediate in heterotypic matings between their parents. The inter-population crosses resulted in significantly lower egg hatching rate and shorter female longevity than intra-population crosses. These results demonstrated that there exist some incompatibilities in premating, postmating-prezygotic, and postzygotic stages between the southern XS population and northern TA population of the cabbage beetle Colaphellus bowringi.

Eliminating turbulence in spatially intermittent flows.

Flows through pipes and channels are the most common means to transport fluids in practical applications and equally occur in numerous natural systems. In general, the transfer of fluids is energetically far more efficient if the motion is smooth and laminar because the friction losses are lower. However, even at moderate velocities pipe and channel flows are sensitive to minute disturbances, and in practice most flows are turbulent. Investigating the motion and spatial distribution of vortices, we uncovered an amplification mechanism that constantly feeds energy from the mean shear into turbulent eddies. At intermediate flow rates, a simple control mechanism suffices to intercept this energy transfer by reducing inflection points in the velocity profile. When activated, an immediate collapse of turbulence is observed, and the flow relaminarizes.