|Table of Contents|

Effects of puerarin on apoptosis of prostate cancer cells through TGF-β/Smads signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2020 01
Page:
17-22
Research Field:
Publishing date:

Info

Title:
Effects of puerarin on apoptosis of prostate cancer cells through TGF-β/Smads signaling pathway
Author(s):
Jin Bei1; Huang Rongfei2; Liu Qingsong3
1.Department of Pathology，Ya’an Yucheng District People’s Hospital，Sichuan Ya’an 625000，China；2.Department of Pathology，the First Affiliated Hospital of Chengdu Medical College，Sichuan Chengdu 610500，China；3.Department of Pathology，Neijiang First People’s Hospital，Sichuan Neijiang 641000，China.
Keywords:
puerarin; TGF-β/Smads; prostate cancer; apoptosis
PACS:
R737.25
DOI:
10.3969/j.issn.1672-4992.2020.01.005
Abstract:
Objective：To investigate the mechanism of puerarin promoting apoptosis of prostate cancer cells through TGF-β/Smads signaling pathway.Methods：Different concentrations of puerarin(0，25，50,75 and 100 μmol/L) were incubated with prostate cancer PC3 cells，respectively，and trypan blue staining was used to detect cell proliferation.Flow cytometry was used to detect different doses of puerarin.The effect of puerarin on TGF-β1 and Smad3 was detected by RT-PCR and Western blot.The expression of TGF-β1 was inhibited by TGF-β1 inhibitor P144，and the expression of TGF-β1 by P144 was confirmed by Western blot.The effect of the content and its effect on the expression levels of the apoptotic proteins Casepase3 and Bcl-2 were detected.Results：Puerarin inhibited the growth of PC3 cells in a time- and dose-dependent manner(P<0.05).The inhibition rates of 25，50，75 and 100 μmol/L puerarin were 25.7%，28.9%，32.5% and 56.3%，respectively.The results of flow cytometry indicated that the apoptosis rates of puerarin on PC3 cells were (4.36±2.62)%，(9.86±3.64)%，(15.95±5.22)%，(19.65±7.34)%.With the increase of dose，the apoptosis rate of PC3 cells increased gradually(P<0.05).RT-PCR and Western blot showed that with the concentration of puerarin elevated，TGF-β1，Smad3 and Caspase3 were highly expressed at mRNA and protein levels significantly，while Bcl-2 was significantly decreased(P<0.05).Compared with puerarin alone，the expression of TGF-β1，Smad3 and Caspase3 protein was significantly decreased in puerarin+P144 co-treatment group，Bcl-2 protein expression level was significantly increased(P<0.05).The results of subsequent flow cytometry showed that the apoptosis level of cells treated with puerarin+P144 was significantly lower than that of puerarin alone(P<0.05).Conclusion：Puerarin can induce apoptosis of PC3 cells by inducing down-regulation of anti-apoptotic protein and activation of Caspase3 by activating TGF-β/Smad receptor signaling pathway.

References:

［1］Zhang Q，Hong B，Wu S，et al.Inhibition of prostatic cancer growth by ginsenoside Rh2［J］.Tumor Biology，2015，36(4)：2377-2381.
［2］Gundem G，Van Loo P，Kremeyer B，et al.The evolutionary history of lethal metastatic prostate cancer［J］.Nature，2015，520(7547)：353.
［3］Chen W，Zheng R，Baade PD，et al.Cancer statistics in China，2015［J］.CA：A Cancer Journal for Clinicians，2016，66(2)：115-132.
［4］Fournier PGJ，Juárez P，Jiang G，et al.The TGF-β signaling regulator PMEPA1 suppresses prostate cancer metastases to bone［J］.Cancer Cell，2015，27(6)：809-821.
［5］Hu Q，Tong S，Zhao X，et al.Periostin mediates TGF-β-induced epithelial mesenchymal transition in prostate cancer cells［J］.Cellular Physiology and Biochemistry，2015，36(2)：799-809.
［6］Seoane J，Gomis RR.TGF-β family signaling in tumor suppression and cancer progression［J］.Cold Spring Harbor Perspectives in Biology，2017，2(02)：277.
［7］Yang F，Chen Y，Shen T，et al.Stromal TGF-β signaling induces AR activation in prostate cancer［J］.Oncotarget，2014，5(21)：10854.
［8］Yuan J，Yang F，Wang F，et al.A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma［J］.Cancer cell，2014，25(5)：666-681.
［9］Li C，Wang Z，Wang Q，et al.Enhanced anti-tumor efficacy and mechanisms associated with docetaxel-piperine combination-in vitro and in vivo investigation using a taxane-resistant prostate cancer model［J］.Oncotarget，2018，9(3)：3338.
［10］Liu X，Zhao W，Wang W，et al.Puerarin suppresses LPS-induced breast cancer cell migration，invasion and adhesion by blockage NF-κB and Erk pathway［J］.Biomedicine & Pharmacotherapy，2017，92(05)：429-436.
［11］Meng XP，Zhang Z，Wang YF，et al.Evaluation of anti-hepatocarcinoma capacity of puerarin nanosuspensions against human HepG2 cells［C］//Biophotonics and Immune Responses XII.International Society for Optics and Photonics，2017（10065）：100650U.
［12］Tamaki H，Harashima N，Hiraki M，et al.Bcl-2 family inhibition sensitizes human prostate cancer cells to docetaxel and promotes unexpected apoptosis under caspase-9 inhibition［J］.Oncotarget，2014，5(22)：11399.
［13］Li Y，Luo W，Li G，et al.Genistein induced apoptosis of gastric cancer cell through Bcl-2 and Caspase-3 regulation［J］.Clin Oncology，2016，51(1)：1150-1156.
［14］K Kontos C，Christodoulou MI，Scorilas A.Apoptosis-related BCL2-family members：Key players in chemotherapy［J］.Anti-Cancer Agents in Medicinal Chemistry(Formerly Current Medicinal Chemistry-Anti-Cancer Agents)，2014，14(3)：353-374.
［15］David CJ，Huang YH，Chen M，et al.TGF-β tumor suppression through a lethal EMT［J］.Cell，2016，164(5)：1015-1030.
［16］Oshimori N，Oristian D，Fuchs E.TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma［J］.Cell，2015，160(5)：963-976.
［17］Neuzillet C，Tijeras-Raballand A，Cohen R，et al.Targeting the TGFβ pathway for cancer therapy［J］.Pharmacology & Therapeutics，2015，147(01)：22-31.
［18］Morikawa M，Derynck R，Miyazono K.TGF-β and the TGF-β family：Context-dependent roles in cell and tissue physiology［J］.Cold Spring Harbor Perspectives in Biology，2016，8(5)：a021873.
［19］Narimatsu M，Samavarchi-Tehrani P，Varelas X，et al.Distinct polarity cues direct Taz/Yap and TGFβ receptor localization to differentially control TGFβ-induced Smad signaling［J］.Developmental Cell，2015，32(5)：652-656.
［20］Wu M，Chen G，Li YP.TGF-β and BMP signaling in osteoblast，skeletal development，and bone formation，homeostasis and disease［J］.Bone Research，2016，4(41)：16009.

Memo

Memo:
四川省卫生和计划生育委员会支助项目（编号：J201800103）
Last Update: 1900-01-01