RESUMEN
Studies have shown chemopreventive and/or chemotherapeutic effects of several curcumin-based combinatorial treatments on colorectal cancer cells. However, their in vivo effects remain unclear. This study has demonstrated the therapeutic effect of curcumin and oxaliplatin, alone or in combination, on subcutaneously xenografted LoVo human colorectal cancer cells in immunodeficient (nu/nu) mice in vivo. Combinatorial administration of curcumin and oxaliplatin evidently inhibited the growth of colorectal cancer in nude mice, which was significantly more effective than either agent alone. Curcumin combined with oxaliplatin treatment induced apoptosis, accompanied by ultrastructural changes and cell cycle arrest in S and G2/M phases. Further mechanism analysis indicated that while the number of apoptotic tumor cells and the expression of Bax, caspase-3, and poly (ADP-ribose) polymerase (PARP) increased significantly, the expression of Bcl-2, survivin, HSP70, pro-caspase-3, and pro-PARP were dramatically suppressed in tumor cells after the treatment with combinatorial curcumin and oxaliplatin for 22 days. Taken together, the present study has demonstrated that administration of combined curcumin and oxaliplatin effectively suppressed colorectal carcinoma in vivo through inducing apoptosis and thus may provide an effective treatment for colorectal carcinoma.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Curcumina/farmacología , Compuestos Organoplatinos/farmacología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Masculino , Ratones , Ratones Desnudos , Oxaliplatino , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Curcumin, a natural plant extract from Curcuma longa, is known for its anti-carcinogenic and chemopreventive effects on a variety of experimental cancer models. In this study, we evaluated the effects of curcumin and elucidated its mechanism in human colorectal carcinoma cells. Cell viability assay showed that curcumin significantly inhibited the growth of LoVo cells. Curcumin treatment induced the apoptosis accompanied by ultra-structural changes and release of lactate dehydrogenase in a dose-dependent manner. Moreover, treatment with 0-30 µg/mL curcumin decreased the mitochondrial membrane potential and activated the caspase-3 and caspase-9 in a dose- and time-dependent manner. Nuclear and annexin V/PI staining showed that curcumin induced the apoptosis of LoVo cells. FACS analysis revealed that curcumin could induce the cell cycle arrest of LoVo cells at the S phase. Furthermore, western blotting analysis indicated that curcumin induced the release of cytochrome c, a significant increase of Bax and p53 and a marked reduction of Bcl-2 and survivin in LoVo cells. Taken together, our results suggested that curcumin inhibited the growth of LoVo cells by inducing apoptosis through a mitochondria-mediated pathway.
Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , Mitocondrias/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcuma/química , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Survivin , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To discuss the biological function and regulation mechanism of curcumin in promoting human colorectal carcinoma (LoVo) cells apoptosis. METHOD: Conventional in vitro culture in human colorectal carcinoma cells LoVo, When 80%-90% confluence was reached, cells were treated with curcumin at different concentrations (0-20 mg x L(-1)). Curcumin's effect on cell proliferation level was examined by MTT colorimetry. The ultrastructure of curcumin-treated LoVo cells were observed with transmission electron microscope (TEM). The amount of PI-positive LoVo cells after the curcumin treatment were determined by flow cytometry. The cell apoptosis rate was detected by Annexin V-FITC/PI double staining. The mRNA level of Bax, Bcl-2, Caspase-3 and Bcl-xL were tested by means of RT-PCR. RESULT: MTT test indicates curcumin could inhibite the growth and proliferation of LoVo cells in a time- and concentration-dependent manner. TEM examination showed that curcumin can make LoVo cell morphological changes, showing the typical characteristics of apoptotic cells. Flow cytometry instrument analysis showed that curcumin can arrest cell cycle at S phase, and induce apoptosis of LoVo cells. RT-PCR test showed that curcumin can activate the expression of Bax and Caspase-3, inhibit the expression of Bcl-2 and Bcl-xL at the mRNA level. CONCLUSION: Curcumin can significantly inhibit the proliferation and induce the apoptosis of human colorectal carcinoma cells LoVo. Such biological effect may be associated with activating Caspase-3 signal channel by activating Bax expression and inhibiting Bcl-2 and Bcl-xL expression. This study lays an important foundation for further discussing the mechanism of curcumin in inducing human colorectal carcinoma LoVo apoptosis.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Curcumina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Relación Dosis-Respuesta a Droga , HumanosRESUMEN
CeO2/Tb4O7 superlattices were deposited on P type Si wafers by e-beam evaporation technology. Four typical photoluminescence peaks of Tb3+ ions which located around 488, 544, 588 and 623 nm were obtained after the superlattices annealing in weak reducing atmosphere at high temperature. It was indicated that CeO2 films transferred to amorphous state as the valence transition of Ce4+ --> Ce3+ which was induced by thermal annealing, the energy transfer occurred between Ce3+ ions and Tb3+ ions, and the Tb3+ ions emition could be detected after obtaining the energy from Ce3+ ions. A study about the effect of Tb4O7 thickness on the superlattices photoluminescence showed that the maximum PL intensity as thickness of Tb4 O7 films were about 0.5 nm, the concentration quenching might occur because of the energy transfer among the Tb3+ ions. The annealing conditions research demonstrated that the maximum PL intensity could be obtained as the superlattices annealed at 1 200 degrees C for 2 hour. Further investigation inferred that the concentration of Ce3+ ions, Oxygen vacancy defects and the distance between Ce3+ ions and Tb3+ ions play an important role in the annealing process.
RESUMEN
BACKGROUND: Close relationships between ticks and microbial communities are important for tick fitness and pathogen colonization and transmission. Haemaphysalis longicornis, distributed widely in China, can carry and transmit various pathogens and pose serious damages to public health and economics. However, little is known about the broader array of microbial communities and symbionts in H. longicornis under natural conditions. In the present study, we investigated the composition of bacterial communities associated with H. longicornis and evaluated the putative symbionts. METHODS: The eubacterial 16S rRNA gene clone libraries of H. longicornis were constructed and analyzed by restriction fragment length polymorphism (RFLP) and DNA sequencing. In addition, diagnostic PCR was performed to assess the prevalence, vertical transmission and infection sites of the symbionts in H. longicornis. RESULTS: Vertically-transmitted symbionts, potential pathogens and allochthonous nonpathogenic bacteria were identified from the field-collected H. longicornis. Three types of symbionts (Coxiella-like, Arsenophonus-like and Rickettsia-like symbionts) were identified in a single host simultaneously. A series of analyses revealed the vertical transmission, prevalence, and infection sites of these symbionts. However, only Coxiella-like bacteria were transmitted stably in the laboratory-reared ticks. In addition, we identified a novel Coxiella-like agent with 95.31% sequence similarity to the taxon described previously. CONCLUSIONS: The present study demonstrated that natural H. longicornis harboured a diverse array of microbial communities. Three types of symbionts were identified in a single host simultaneously. Moreover, high prevalence, vertical transmission and the infection sites supported an obligate symbiotic association between Coxiella symbiont and its host. The role of Coxiella symbiont in the host fitness and the interaction among microbial communities remained to be elucidated. Our investigation of microbial communities in the ticks revealed the complexity of ecological interactions between host and microbe and provided insight for the biological control of ticks.