1.Anti-cutaneous squamous cell carcinoma effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m
Shanshan TANG ; Dongyun RONG ; Ye WANG ; Yushen SU ; Tao WANG ; Qiu LONG ; Yu CAO
China Pharmacy 2023;34(9):1086-1092
OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects, CCK-8 assay was used to detect the effects of different concentrations of 3m (5, 10, 20, 40, 80 μmol/L) on the proliferation of A431 and Colo-16 cells after 24, 48 and 72 hours; the median inhibitory concentration (IC50) was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group, 3m low-concentration and high- concentration groups (15, 30 μmol/L). After treated with relevant drugs or culture medium for 48 h, the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate, migration rate and number of cell invasions, cell cycle distribution and apoptosis rate were detected. The phosphorylation, or expression of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway related proteins [JAK2, STAT3, B-cell lymphocyte-2 (Bcl-2), Bcl-2- associated X protein (Bax)], and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24, 48, 72 h (P<0.01), and IC50 of them were 20.36, 23.72 μmol/L, respectively. After 48 hours of treatment, compared with control group, A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate, migration rate, number of cell invasions, mRNA expressions of JAK2, STAT3 and Bcl-2, the phosphorylation of JAK2 and STAT3, protein expression of Bcl-2 were significantly decreased/weakened (P<0.01). Proportion of cell cycle in G2 phase, apoptosis rate, protein and mRNA expression of Bax were increased significantly (P<0.01); and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation, clone formation, migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner, the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway, and inducing cell apoptosis.
2.Study on the Effects and Its Mechanism of Sinapine Thiocyanate on the Proliferation ,Epithelial Mesenchymal Transition and Metastasis of Human Cutaneous Squamous Cell Carcinoma SCL- 1 Cells
Yushen SU ; Zhirui ZENG ; Dongyun RONG ; Ye WANG ; Dan LI ; Shanshan TANG ; Tao WANG ; Xuemei LONG ; Yu CAO
China Pharmacy 2021;32(8):952-960
OBJECTIVE:To stud y the effects of sinapine thiocyanate (ST) on the proliferation ,epithelial mesenchymal transformation(EMT)and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells,and to investigate its possible mechanism. METHODS :Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group (0.1% DMSO) and ST different concentration groups (5,10,20 μmol/L). CCK- 8 assay,5-ethynyl-2′-deoxyuridine(EDU)test, scratch test and Transwell chamber invasion test were adopted to test the proliferation ,migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group (0.1% DMSO),ST group (20 μmol/L),ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155(EGFR agonist )] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79(PI3K/Akt agonist )]. The proliferation ,migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay,scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor (EGFR),phosphatidylinositol 3 kinase(PI3K),phosphorylated phosphatidylinositol 3 kinase(p-PI3k),protein kinase B (Akt)and phosphorylated protein Akt (p-Akt)protein of cells in blank control group and ST different concentration groups(5,10,20 μmol/L)were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group (0.1% DMSO),ST group (20 μmol//L),ZD1839 group(positive control ,20 μmol//L,EGFR inhibitor )and LY 294002 group(positive control,20 μmol//L,PI3K/Akt inhibitor ). CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS :Compared with blank control group ,the proliferation ,migration and invasion ability of SCL- 1 cells were significantly decreased in 5,10,20 μmol/L ST groups(P<0.05). Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5,10,20 μmol/L ST groups(P<0.05),while the protein expression of E-cadherin was increased significantly (P<0.05);the protein expressions of EGFR ,p-PI3K and p-Akt were significantly decreased (P<0.05). Compared with ST group ,the proliferation ,migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group (P<0.05). Compared with blank control group ,the proliferation ability of WS 1 cells had no significant change in ST group ,while the proliferation ability of SCL- 1 cells was decreased significantly (P<0.05);the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group(P<0.05). Compared with ST group ,the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group(P<0.05),but there was no significant difference in the proliferation ability of SCL- 1 cells (P>0.05). CONCLUSIONS :ST may inhibit the proliferation ,EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ,and its side effects are few.
3.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850
177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.