Effects of Decursin on Proliferation and Migration of Colorectal Cancer Cells via Upregulation of miR-17-5p through Targeted Regulation of PI3K/Akt Pathway

doi:10.3870/j.issn.1672-0741.24.08.036

Abstract

Abstract: Objective To investigate the effects of Decursin(DE)on the proliferation and migration of colorectal cancer cells and the underlying mechanism. Methods Third-generation SW480 and HCoEpiC cells were selected for the experiment,and the expression of miR-17-5p RNA in the two cell lines was detected via qRT-PCR.The proliferation of SW480 cells was detected via the CCK-8 method at different DE concentrations(0,10,30,60 and 100 μmol/L),and the appropriate concentration of DE was selected.qRT-PCR was used to detect the transfection efficiency of miR-17-5p in SW480 cells.The proliferation of the transfected cells was detected via CCK-8 method,and the number of migrating cells was detected via Transwell experiment.The expression of miR-17-5p was detected via qRT-PCR,the cell proliferation activity was detected via the CCK-8 method,the number of migrating cells was detected via Transwell experiment,and the levels of PIK3R1,p-PI3K,PI3K and p-Akt were detected via Western blotting.The dual-luciferase reporter assay was used to detect the targeting effect of miR-17-5p on PI3K. Results The expression level of miR-17-5p RNA in W480 cells was greater than that in HCoEpiC cells(P<0.05).The proliferation of SW480 cells decreased with increasing DE concentration in a concentration-dependent manner(P<0.05).For the subsequent experiments,60 μmol/L DE was selected.The miR-17-5p mimic/inhibitor significantly increased/decreased the expression of miR-17-5p,cell proliferation activity and the number of migrating cells(P<0.05).After treatment with DE,the expression of miR-17-5p,cell proliferation activity,cell migration,and p-PI3K and p-Akt proteins decreased(P<0.05),whereas the expression of the PIK3R1 protein increased(P<0.05);however,the expression of the PI3K and Akt proteins did not change significantly.When miR-17-5p and Wt-PIK3R1 were co-transfected,the relative luciferase activity decreased/increased with increasing/decreasing miR-17-5p expression(P<0.05).When miR-17-5p and Mut-Wt-PIK3R1 were co-transfected,the relative activity of luciferase did not change significantly(P> 0.05). Conclusion Decursin can inhibit the proliferation and migration of colorectal cancer cells,which may inhibit the PI3K/Akt pathway by downregulating miR-17-5p and promoting the expression of PIK3R1.

Key words: colorectal cancer, Decursin, cell proliferation, cell migration, miR-17-5p

CLC Number:

R735.3

Lv Jiudi, Peng Xin, Xing Yuguang et al. Effects of Decursin on Proliferation and Migration of Colorectal Cancer Cells via Upregulation of miR-17-5p through Targeted Regulation of PI3K/Akt Pathway[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(1): 76-81.

References

[1] Dekker E,Tanis P J,Vleugels J L A,et al.Colorectal cancer[J].Lancet,2019,394(10207):1467-1480.
[2] 唐晋,彭超华,陈雪梅,等.紫花前胡素对百草枯中毒大鼠急性肾损伤的保护作用及肾组织HSF1表达的影响[J].中国中西医结合肾病杂志,2020,21(9):759-763,847.
Tang J,Peng C H,Chen X M,et al.Protective effect of decursin on acute renal injury and expression of HSF1 in renal tissue of paraquat poisoned rats[J].Chinese Journal of Integrated Traditional and Western Nephrology,2020,21(9):759-763,847.
[3] 王慧,邵义熊,阮自琴,等.紫花前胡素经Nox1/Akt信号通路对口腔鳞癌细胞增殖及侵袭的抑制作用[J].中国药业,2019,28(22):10-13.
Wang H,Shao Y X,Ruan Z Q,et al.Inhibition effect of decursin on proliferation and invasion of oral squamous cell carcinoma cells via Nox1/Akt signaling pathway[J].China Pharmaceuticals,2019,28(22):10-13.
[4] 杨懿,胡艳娥,赵茂源,等.紫花前胡素通过PI3K/Akt信号通路影响结直肠癌细胞增殖、凋亡及迁移[J].中国中药杂志,2023,48(9):2334-2342.
Yang Y,Hu Y E,Zhao M Y,et al.Decursin affects proliferation,apoptosis,and migration of colorectal cancer cells through PI3K/Akt signaling pathway[J].China Journal of Chinese Materia Medica,2023,48(9):2334-2342.
[5] Li P,Zhou D,Chen D,et al.Tumor-secreted IFI35 promotes proliferation and cytotoxic activity of CD8⁺ T cells through PI3K/AKT/mTOR signaling pathway in colorectal cancer[J].J Biomed Sci,2023,30(1):47.
[6] Qiao T Y,Yuan Z M,Ma T Y,et al.Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway[J].Neoplasma,2021,68(5):947-954.
[7] Chen M,Tan A H,Li J.Curcumin represses colorectal cancer cell proliferation by triggering ferroptosis via PI3K/Akt/mTOR signaling[J].Nutr Cancer,2023,75(2):726-733.
[8] Zhang L,Chen H,Song Y,et al.MiR-325 promotes oxaliplatin-induced cytotoxicity against colorectal cancer through the HSPA12B/PI3K/AKT/bcl-2 pathway[J].Dig Dis Sci,2021,66(8):2651-2660.
[9] Liu Z,Ji M,Jin F,et al.Expression and clinical significance of miR-17-5p in tumor tissues of patients with colorectal cancer[J].J Gastrointest Oncol,2022,13(6):3067-3079.
[10] Wang Y,Zhao J,Wang Y,et al.miR-17-5p targets and downregulates CADM2,activating the malignant phenotypes of colon cancer cells[J].Mol Biotechnol,2022,64(12):1388-1400.
[11] 郭金兰,甘才斌,张洁,等.miR-17-5p靶向PI3K/AKT信号通路调控皮肤鳞状细胞癌细胞增殖、凋亡的机制[J].中国老年学杂志,2021,41(12):2599-2603.
Guo J L,Gan C B,Zhang J,et al.Mechanism of miR-17-5p targeting PI3K/AKT signaling pathway to regulate proliferation and apoptosis of skin squamous cell carcinoma cells[J].Chinese Journal of Gerontology,2021,41(12):2599-2603.
[12] 任璐,曹芹雪,杨少琴.紫花前胡苷调控EMT对宫颈癌细胞侵袭迁移的影响及其作用机制[J].解放军医学杂志,2022,47(5):451-457.
Ren L,Cao Q X,Yang S Q.Mechanism and effect of nodakenin regulating EMT on the invasion and migration of cervical cancer cells[J].Medical Journal of Chinese People’s Liberation Army,2022,47(5):451-457.
[13] Bhat T A,Dheeraj A,Nambiar D K,et al.Decursin inhibits EGFR-ERK1/2 signaling axis in advanced human prostate carcinoma cells[J].Prostate,2023,83(6):534-546.
[14] Han K,Wang F W,Cao C H,et al.CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17[J].Mol Cancer,2020,19(1):60.
[15] Yilmaz U,Yilmaz N,Tanbek K,et al.Differential expression of miRNAs related to autophagy pathway in tissue and serum samples of colorectal cancer patients[J].Bratisl Lek Listy,2022,123(9):634-640.
[16] Li J,Jiang J L,Chen Y M,et al.KLF2 inhibits colorectal cancer progression and metastasis by inducing ferroptosis via the PI3K/AKT signaling pathway[J].J Pathol Clin Res,2023,9(5):423-435.
[17] Su W,Feng B,Hu L,et al.MUC3 A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway[J].BMC Cancer,2022,22(1):602.
[18] Wang J X,Jia X J,Liu Y,et al.Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma[J].Cancer Cell Int,2020,20:14.
[19] Chakraborty G,Nandakumar S,Hirani R,et al.The impact of PIK3R1 mutations and insulin-PI3K-glycolytic pathway regulation in prostate cancer[J].Clin Cancer Res,2022,28(16):3603-3617.
[20] Song N,Li Y,Cheng J,et al.Study on the molecular mechanism of nightshade in the treatment of colon cancer[J].Bioengineered,2022,13(1):1575-1589.
[21] Zhang Y,Lv P,Ma J,et al.Antrodia cinnamomea exerts an anti-hepatoma effect by targeting PI3K/AKT-mediated cell cycle progression in vitro and in vivo[J].Acta Pharm Sin B,2022,12(2):890-906.
[22] Qu L,Liu Y,Deng J,et al.Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma[J].J Pharm Anal,2023,13(5):463-482.