Oxaliplatin is a key drug in chemotherapy of colorectal cancer （CRC）. However, its efficacy is unsatisfied due to drug resistance of cancer ceils. In this study, we tested whether a natural agent, ursolic acid, was ...Oxaliplatin is a key drug in chemotherapy of colorectal cancer （CRC）. However, its efficacy is unsatisfied due to drug resistance of cancer ceils. In this study, we tested whether a natural agent, ursolic acid, was able to enhance the efficacy of oxaliplatin for CRC. Four CRC cell lines including SW480, SW620, LoVo, and RKO were used as in vitro models, and a SW620 xenograft mouse model was used in further in vivo study. We found that ursolic acid inhibited proliferation and induced apoptosis of all four cells and enhanced the cytotoxicity of oxaliplatin. This effect was associated with down-regulation of Bcl-xL, Bcl-2, survivin, activation of caspase-3, 8, 9, and inhibition of KRAS expression and BRAF, MEKll2, ERK1/2, p-38, JNK, AKT, IKKa, IKBa, and p65 phosphorylation of the MAPK, PI3K/AKT, and NF-KB signaling pathways. The two agents also showed synergistic effects against tumor growth in vivo. In addition, ursolic acid restored liver function and body weight of the mice treated with oxaliplatin. Thus, we concluded that ursolic acid could enhance the therapeutic effects of oxaliplatin against CRC both in vitro and in vivo, which offers an effective strategy to minimize the burden of oxaliplatin-induced adverse events and provides the groundwork for a new clinical strategy to treat CRC.展开更多
The simplification of localized surface plasmon resonance(LSPR) detection can further promote the development of optical biosensing application in point-of-care testing. In this study, we proposed a simple light emitt...The simplification of localized surface plasmon resonance(LSPR) detection can further promote the development of optical biosensing application in point-of-care testing. In this study, we proposed a simple light emitting diode(LED) based single-wavelength LSPR sensor modulated with bio-electron transfers for the detection of electroactive biomolecules. Indium tin oxide electrode loaded with nanocomposites of polyaniline coated gold nanorod was used as LSPR chip, and the applied electric potential was scanned at the LSPR chip for single-wavelength LSPR biosensing. Under the scanning of applied potentials, biological electron transfer of redox reaction was employed to demonstrate the bioelectronic modulation of single-wavelength LSPR for selective electroactive biomolecule detection. Without any additional recognition material, electroactive biomolecules uric acid and dopamine were detected directly with a sensitivity of 5.05 μmol/L and 7.11 μmol/L at their specific oxidation potentials, respectively. With the simplified optical configuration and selective bioelectronic modulation, the single-wavelength LSPR sensor is promising for the development of simple, low-cost, and high specificity optical biosensor for point-of-care testing of electroactive biomolecules.展开更多
文摘Oxaliplatin is a key drug in chemotherapy of colorectal cancer （CRC）. However, its efficacy is unsatisfied due to drug resistance of cancer ceils. In this study, we tested whether a natural agent, ursolic acid, was able to enhance the efficacy of oxaliplatin for CRC. Four CRC cell lines including SW480, SW620, LoVo, and RKO were used as in vitro models, and a SW620 xenograft mouse model was used in further in vivo study. We found that ursolic acid inhibited proliferation and induced apoptosis of all four cells and enhanced the cytotoxicity of oxaliplatin. This effect was associated with down-regulation of Bcl-xL, Bcl-2, survivin, activation of caspase-3, 8, 9, and inhibition of KRAS expression and BRAF, MEKll2, ERK1/2, p-38, JNK, AKT, IKKa, IKBa, and p65 phosphorylation of the MAPK, PI3K/AKT, and NF-KB signaling pathways. The two agents also showed synergistic effects against tumor growth in vivo. In addition, ursolic acid restored liver function and body weight of the mice treated with oxaliplatin. Thus, we concluded that ursolic acid could enhance the therapeutic effects of oxaliplatin against CRC both in vitro and in vivo, which offers an effective strategy to minimize the burden of oxaliplatin-induced adverse events and provides the groundwork for a new clinical strategy to treat CRC.
基金the National Natural Science Foundation of China (Nos. 81971703, 81801793, 31671007)the China Postdoctoral Science Foundation (Nos. 2018M630677, 2019T120518)+3 种基金the National Key Research and Development Program (No. 2018YFC1707701)the Zhejiang Provincial Natural Science Foundation of China (No. LZ18C100001)the Fundamental Research Funds for the Central Universities (Nos. 2021QNA5018, 2021FZZX002-05)the Collaborative Innovation Center of Traditional Chinese Medicine Health Management of Fujian Province of China。
文摘The simplification of localized surface plasmon resonance(LSPR) detection can further promote the development of optical biosensing application in point-of-care testing. In this study, we proposed a simple light emitting diode(LED) based single-wavelength LSPR sensor modulated with bio-electron transfers for the detection of electroactive biomolecules. Indium tin oxide electrode loaded with nanocomposites of polyaniline coated gold nanorod was used as LSPR chip, and the applied electric potential was scanned at the LSPR chip for single-wavelength LSPR biosensing. Under the scanning of applied potentials, biological electron transfer of redox reaction was employed to demonstrate the bioelectronic modulation of single-wavelength LSPR for selective electroactive biomolecule detection. Without any additional recognition material, electroactive biomolecules uric acid and dopamine were detected directly with a sensitivity of 5.05 μmol/L and 7.11 μmol/L at their specific oxidation potentials, respectively. With the simplified optical configuration and selective bioelectronic modulation, the single-wavelength LSPR sensor is promising for the development of simple, low-cost, and high specificity optical biosensor for point-of-care testing of electroactive biomolecules.
