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| 1 | Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes显示文摘Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects. | Bingtao Zhai Qibiao Wu Wengang Wang Mingming Zhang Xuemeng Han Qiujie Li Peng Chen Xiaying Chen Xingxing Huang Guohua Li Qin Zhang Ruonan Zhang Yu Xiang Shuiping Liu Ting Duan Jianshu Lou Tian Xie Xinbing Sui | 2020 | Cancer Biology & Medicine2020，17，1： | 6 |
| 2 | PCDH17 increases the sensitivity of colorectal cancer to 5-fluorouracil treatment by inducing apoptosis and autophagic cell death显示文摘5-Fluorouracil(5-FU)is known as a first-line chemotherapeutic agent against colorectal cancer(CRC),but drug resistance occurs frequently and significantly limits its clinical success.Our previous study showed that the protocadherin 17(PCDH17)gene was frequently methylated and functioned as a tumor suppressor in CRC.However,the relationship between PCDH17 and 5-FU resistance in CRC remains unclear.Here,we revealed that PCDH17 was more highly expressed in 5-FU-sensitive CRC tissues than in 5-FU-resistant CRC tissues,and high expression of PCDH17 was correlated with high BECN1 expression.Moreover,this expression profile contributed to superior prognosis and increased survival in CRC patients.Restoring PCDH17 expression augmented the 5-FU sensitivity of CRC in vitro and in vivo by promoting apoptosis and autophagic cell death.Furthermore,autophagy played a dominant role in PCDH17-induced cell death,as an autophagy inhibitor blocked cell death to a greater extent than the pancaspase inhibitor Z-VAD-FMK.PCDH17 inhibition by siRNA decreased the autophagy response and 5-FU sensitivity.Mechanistically,we showed that c-Jun NH2-terminal kinase(JNK)activation was a key determinant in PCDH17-induced autophagy.The compound SP600125,an inhibitor of JNK,suppressed autophagy and 5-FU-induced cell death in PCDH17-reexpressing CRC cells.Taken together,our findings suggest for the first time that PCDH17 increases the sensitivity of CRC to 5-FU treatment by inducing apoptosis and JNK-dependent autophagic cell death.PCDH17 may be a potential prognostic marker for predicting 5-FU sensitivity in CRC patients. | Shuiping Liu Haoming Lin Da Wang Qiang Li Hong Luo Guoxiong Li Xiaohui Chen Yongqiang Li Peng Chen Bingtao Zhai Wengang Wang Ruonan Zhang Bi Chen Mingming Zhang Xuemeng Han Qiujie Li Liuxi Chen Ying Liu Xiaying Chen Guohua Li Yu Xiang Ting Duan Jiao Feng Jianshu Lou Xingxing Huang Qin Zhang Ting Pan Lili Yan Ting Jin Wenzheng Zhang Lvjia Zhuo Yitian Sun Tian Xie Xinbing Sui | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 4 |
| 3 | Simultaneous NF‐κB inhibition and E‐cadherin upregulation mediate mutually synergistic anticancer activity of celastrol and SAHA in vitro and in vivo显示文摘 | Lin Zheng Yingying Fu Linhan Zhuang Renhua Gai Jian Ma Jianshu Lou Hong Zhu Qiaojun He Bo Yang | 2014 | Int. J. Cancer2014，，： | 1 |
| 4 | pPeOp inhibits HGC-27 cell proliferation,migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway显示文摘Gastric cancer is the fifth most frequently occurring and the fourth most lethal malignant cancer worldwide.A bioactive protein(pPeOp)from Omphalia lapidescens exhibits significant inhibitory effects on gastric cancer cells.miRNA deep sequencing analysis shows that miR-30b-5p is significantly upregulated in HGC-27 cells treated with pPeOp.Verification results show that the expression level of miR-30b-5p is significantly increased in HGC-27 cells after pPeOp treatment.Additionally,miR-30b-5p is significantly downregulated in clinical gastric cancer tissues compared to that in adjacent normal tissues.Following pPeOp treatment and/or transfection with miR-30b-5p mimic,the proliferation,migration,and invasion of HGC-27 cells are significantly impaired.Immunofluorescence microscopy shows that pPeOp and/or miR-30b-5p destroy(s)microfilaments and microstructures and inhibit(s)the formation of pseudopodia.Bioinformatics analysis,dual-luciferase reporter assay,and western blot analysis confirm that miR-30b-5p downregulates Rac1/Cdc42 expression and activation by targeting RAB22A.Available data indicate that miR-30b-5p plays an anti-gastric cancer role in mediating pPeOp.pPeOp upregulates miR-30b-5p expression,which in turn inhibits RAB22A expression,resulting in a reduction in the expression and activation of Rac1 and Cdc42 and their downstream targets,thus destroying the cytoskeletal structure and inhibiting the proliferation,migration,and invasion of cancer cells. | Wenjun Xu Zhenjie Fu Yuqin Xu Man Hei Cheung Yan Chen Meiai Lin Hang Wen Hang Lv Chun Liang Jianshu Lou Yitao Chen | 2022 | Acta Biochimica et Biophysica Sinica2022，54，12： | 0 |
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