Inhibition of miR-141 reverses cisplatin resistance in non-small cell lung cancer cells via upregulation of programmed cell death protein 4.

OBJECTIVE: MicroRNAs are a class of essential regulators in cancer, and previous studies have shown that miR-141 is a tumor suppressor in non-small cell lung cancer (NSCLC). However, it is still unknown whether it regulates chemosensitivity. We aimed to investigate the role of miR-141 in cisplatin resistance in NSCLC cells. MATERIALS AND METHODS: MiR-141 expression in A549 and A549/DDP cell lines have been quantified by real-time PCR. Protein level of PDCD4 and caspase-3 have been determined by Western blot analysis. Drug sensitivity and apoptosis have been determined by MTT assay and TUNEL assay, respectively. Luciferase activity assay was employed to validate the relationship between 3'UTR of PDCD4 mRNA and miR-141. RESULTS: We observed that miR-141 expression was significantly up-regulated in cisplatin-resistant A549/DDP cells compared with the parental cell line A549; and PDCD4, an important apoptosis regulator, was found to be down-regulated. Luciferase activity assay and Western blot analysis confirmed that PDCD4 is a direct target of miR-141. Inhibition of miR-141 in A549/DDP cells markedly increased cisplatin sensitivity and apoptosis, which was partially abrogated by PDCD4 inhibition, indicating that PDCD4 is a functional target of miR-141 in of the regulation of cisplatin sensitivity. CONCLUSIONS: Our data showed that miR-141 participates in regulating cisplatin sensitivity in non-small lung cancer cells via PDCD4 inhibition, and suppression of miR-141 might be a therapeutic method to overcome cisplatin resistance in clinical practice.

Substrate-Binding reactions of the 3[dsigma*psigma] excited state of binuclear gold(I) complexes with bridging bis(dicyclohexylphosphino)methane ligands: emission and time-resolved absorption spectroscopic studies.

The complexes [Au2(dcpm)2]-Y2 (dcpm = bis(dicyclohexylphosphino)methane; Y=ClO4 (1), PF6- (2), CF3SO3- (3), Au(CN)2- (4), Cl- (5), SCN (6) and I- (7)) were prepared, and the structures of 1 and 4-7 were determined by X-ray crystallography. Complexes 1-4 display intense phosphorescence with lambdamax at 360-368 nm in the solid state at room temperature as well as in glassy solutions at 77 K. The solid-state emission quantum yields of the powdered samples are 0.37 (1), 0.74 (2), 0.53 (3) and 0.12 (4). Crystalline solid 5 displays both high-energy UV (lambdamax = 366 nm) and low-energy visible emissions (lambdamax = 505 nm) at room temperature, whereas either 6 or 7 shows only an intense emission with lambdamax at 465 or 473 nm, respectively. All the complexes in degassed acetonitrile solutions exhibit an intense phosphorescence with lambdamax ranging from 490 to 530 nm. The high-energy UV emission is assigned to the intrinsic emission of the 3[dsigma*psigma] excited state of [Au2(dcpm)2]2+, whereas the visible emission is attributed to the adduct formation of the triplet excited state with the solvent/counterion. The quenching rate constants of the visible emission of [Au2(dcpm)2]2+ in acetonitrile by various anions are 6.08 x 10(5) (ClO4-), 9.18 x l0(5) (PF6 ), 1.55 x 10(7) (Cl-) and 4.06 x 10(9) (I-) mol(-1) dm3s(-1). The triplet-state difference absorption spectra of 1-4 in acetonitrile show an absorption band with lambdamax at 350 nm and a shoulder/absorption maxima at 395-420 nm; their relative intensities are dependent upon the halide ion present in solution. Substrate binding reactions of the 3[dsigma*psigma] excited state with halide (X-) to give [Au2(dcpm)2X]+* would account for the lower energy absorption maxima in the triplet-state difference absorption spectra. With iodide as the counterion, complex 7 undergoes a photoinduced electron-transfer reaction with I- to give the radical anion I2-.