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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2024

Open Access 01-12-2024 | SCLC | Research

Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells

Authors: Yuxin Jiang, Yanli Bi, Lingjie Zhou, Senwen Zheng, Tingting Jian, Jian Chen

Published in: BMC Complementary Medicine and Therapies | Issue 1/2024

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Abstract

Background

Small cell lung cancer (SCLC) is the most malignant lung cancer type. Due to the high rates of metastasis and drug resistance, effective therapeutic strategies remain lacking. Tanshinone IIA (Tan IIA) has been reported to exhibit anti-tumor activity. Therefore, this study investigated the ability and underlying mechanism of Tan IIA to inhibit the metastasis and proliferation of SCLC.

Methods

H1688 and H446 cells were treated in vitro with Tan IIA (0, 1, 2 and 4 µM) or LY294002 (10 µM) for 24, 48, 72 h. H1688 and H446 cell migration was evaluated in wound healing and transwell migration assays. RNA-sequencing helped assess gene expression. BALB/c nude mice were injected with H1688 cells and treated with the Tan IIA group (10 mg/kg/day) or a control. Expression of E-cadherin, vimentin and PI3K/Akt signaling pathway proteins in tumors and H1688 was investigated by immunohistochemical analysis and western blot.

Results

Tan IIA inhibited H1688 and H446 cell proliferation without inducing apoptosis and suppressed H1688 and H446 cell migration. E-cadherin expression was increased, while vimentin expression was reduced after administration of Tan IIA. RNA-sequencing revealed that some genes related with the PI3K/Akt signaling pathway were altered using Tan IIA treatment. Furthermore, western blot helped detect PI3K and p-Akt expression was also reduced by Tan IIA treatment. Tan IIA inhibited tumor growth in vivo. Moreover, Tan IIA increased tumoral expression of E-cadherin accompanied by PI3K and p-Akt downregulation.

Conclusion

Tan IIA suppresses SCLC proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway, thereby highlighting the potential of Tan IIA as a new and relatively safe drug candidate to treat SCLC.
Appendix
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Literature
1.
Hong QY, Wu GM, Qian GS, Hu CP, Zhou JY, Chen LA, Li WM, Li SY, Wang K, Wang Q, et al. Prevention and management of lung cancer in China. Cancer. 2015;121(Suppl 17):3080–8.CrossRefPubMed
2.
Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer 2015, 121(5):664–72.
3.
Sun A, Durocher-Allen LD, Ellis PM, Ung YC, Goffin JR, Ramchandar K, Darling G. Initial management of small-cell lung cancer (limited- and extensive-stage) and the role of thoracic radiotherapy and first-line chemotherapy: a systematic review. Curr Oncol. 2019;26(3):e372–84.CrossRefPubMedPubMedCentral
4.
Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer. 2017;17(12):725–37.CrossRefPubMed
5.
Wang K, Chen Q, Shao Y, Yin S, Liu C, Liu Y, Wang R, Wang T, Qiu Y, Yu H. Anticancer activities of TCM and their active components against tumor metastasis. Biomed Pharmacother. 2021;133:111044.CrossRefPubMed
6.
Chen Y, Yu M, Liu Z, Zhang Y, Li Q, Yang G. Effects of traditional Chinese medicine combined with chemotherapy for extensive-stage small-cell lung cancer patients on improving oncologic survival: study protocol of a multicenter, randomized, single-blind, placebo-controlled trial. Trials. 2021;22(1):437.CrossRefPubMedPubMedCentral
7.
Xu XQ, Deng WQ, Wang DY, Li M, Kou DL, Zhang PT. Chinese Medicine treatment prolonged Survival in Small Cell Lung Cancer patients: a Clinical Observation. Chin J Integr Med. 2021;27(7):496–501.CrossRefPubMed
8.
Zeng P, Li J, Chen Y, Zhang L. The structures and biological functions of polysaccharides from traditional Chinese herbs. Prog Mol Biol Transl Sci. 2019;163:423–44.CrossRefPubMedPubMedCentral
9.
Zhu B, Zhang QL, Hua JW, Cheng WL, Qin LP. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: a review. J Ethnopharmacol. 2018;226:143–67.CrossRefPubMed
10.
Zhang W, Liu C, Li J, Lu Y, Li H, Zhuang J, Ren X, Wang M, Sun C. Tanshinone IIA: New Perspective on the Anti-tumor mechanism of a traditional Natural Medicine. Am J Chin Med. 2022;50(1):209–39.CrossRefPubMed
11.
Chen J, Bi Y, Chen L, Zhang Q, Xu L. Tanshinone IIA exerts neuroprotective effects on hippocampus-dependent cognitive impairments in diabetic rats by attenuating ER stress-induced apoptosis. Biomed Pharmacother. 2018;104:530–6.CrossRefPubMed
12.
Guo R, Li L, Su J, Li S, Duncan SE, Liu Z, Fan G. Pharmacological activity and mechanism of Tanshinone IIA in Related diseases. Drug Des Devel Ther. 2020;14:4735–48.CrossRefPubMedPubMedCentral
13.
Ko J, Winslow MM, Sage J. Mechanisms of small cell lung cancer metastasis. EMBO Mol Med. 2021;13(1):e13122.CrossRefPubMed
14.
Jin K, Li T, van Dam H, Zhou F, Zhang L. Molecular insights into tumour metastasis: tracing the dominant events. J Pathol. 2017;241(5):567–77.CrossRefPubMed
15.
Krencz I, Sztankovics D, Danko T, Sebestyen A, Khoor A. Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations. Cancer Metastasis Rev. 2021;40(4):1141–57.CrossRefPubMedPubMedCentral
16.
Yeh J, Litz J, Hauck P, Ludwig DL, Krystal GW. Selective inhibition of SCLC growth by the A12 anti-IGF-1R monoclonal antibody correlates with inhibition of Akt. Lung Cancer. 2008;60(2):166–74.CrossRefPubMed
17.
Liu H, Liu C, Wang M, Sun D, Zhu P, Zhang P, Tan X, Shi G. Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway. Sci Rep. 2021;11(1):19268.CrossRefPubMedPubMedCentral
18.
Wang N, Zhang X, Ma Z, Niu J, Ma S, Wenjie W, Chen J. Combination of tanshinone IIA and astragaloside IV attenuate atherosclerotic plaque vulnerability in ApoE(-/-) mice by activating PI3K/AKT signaling and suppressing TRL4/NF-kappaB signaling. Biomed Pharmacother. 2020;123:109729.CrossRefPubMed
19.
Deng H, Yu B, Li Y. Tanshinone IIA alleviates acute ethanol-induced myocardial apoptosis mainly through inhibiting the expression of PDCD4 and activating the PI3K/Akt pathway. Phytother Res. 2021;35(8):4309–23.CrossRefPubMed
20.
Xu L, Bi Y, Xu Y, Zhang Z, Xu W, Zhang S, Chen J. Oridonin inhibits the migration and epithelial-to-mesenchymal transition of small cell lung cancer cells by suppressing FAK-ERK1/2 signalling pathway. J Cell Mol Med. 2020;24(8):4480–93.CrossRefPubMedPubMedCentral
21.
Xu L, He D, Wu Y, Shen L, Wang Y, Xu Y. Tanshinone IIA inhibits cardiomyocyte apoptosis and rescues cardiac function during doxorubicin-induced cardiotoxicity by activating the DAXX/MEK/ERK1/2 pathway. Phytomedicine. 2022;107:154471.CrossRefPubMed
22.
Raso MG, Bota-Rabassedas N, Wistuba II. Pathology and classification of SCLC. Cancers (Basel) 2021, 13(4).
23.
24.
Tseng PY, Lu WC, Hsieh MJ, Chien SY, Chen MK. Tanshinone IIA induces apoptosis in human oral cancer KB cells through a mitochondria-dependent pathway. Biomed Res Int. 2014;2014:540516.CrossRefPubMedPubMedCentral
25.
Xie S, Wu Z, Qi Y, Wu B, Zhu X. The metastasizing mechanisms of lung cancer: recent advances and therapeutic challenges. Biomed Pharmacother. 2021;138:111450.CrossRefPubMed
26.
27.
Li S, Qin X, Chai S, Qu C, Wang X, Zhang H. Modulation of E-cadherin expression promotes migration ability of esophageal cancer cells. Sci Rep. 2016;6:21713.CrossRefPubMedPubMedCentral
28.
29.
30.
He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, Li B. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 2021;6(1):425.CrossRefPubMedPubMedCentral
31.
Zhang FY, Hu Y, Que ZY, Wang P, Liu YH, Wang ZH, Xue YX. Shikonin inhibits the Migration and Invasion of Human Glioblastoma cells by targeting phosphorylated beta-catenin and phosphorylated PI3K/Akt: a potential mechanism for the Anti-glioma Efficacy of a traditional Chinese Herbal Medicine. Int J Mol Sci. 2015;16(10):23823–48.CrossRefPubMedPubMedCentral
32.
Hao Y, Zhang C, Sun Y, Xu H. Licochalcone A inhibits cell proliferation, migration, and invasion through regulating the PI3K/AKT signaling pathway in oral squamous cell carcinoma. Onco Targets Ther. 2019;12:4427–35.CrossRefPubMedPubMedCentral
33.
Tseng YH, Yang CC, Lin SC, Cheng CC, Lin SH, Liu CJ, Chang KW. Areca nut extract upregulates vimentin by activating PI3K/AKT signaling in oral carcinoma. J Oral Pathol Med. 2011;40(2):160–6.CrossRefPubMed
34.
Xu E, Xia X, Jiang C, Li Z, Yang Z, Zheng C, Wang X, Du S, Miao J, Wang F, et al. Corrigendum: GPER1 silencing suppresses the Proliferation, Migration, and Invasion of Gastric Cancer cells by inhibiting PI3K/AKT-Mediated EMT. Front Cell Dev Biol. 2022;10:841792.CrossRefPubMedPubMedCentral
35.
36.
Teng Z, Xu S, Lei Q. Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB152 in vivo and in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway. Oncol Rep. 2020;43(2):503–15.PubMed
37.
Su CC, Chiu TL. Tanshinone IIA decreases the protein expression of EGFR, and IGFR blocking the PI3K/Akt/mTOR pathway in gastric carcinoma AGS cells both in vitro and in vivo. Oncol Rep. 2016;36(2):1173–9.CrossRefPubMed
Metadata
Title
Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells
Authors
Yuxin Jiang
Yanli Bi
Lingjie Zhou
Senwen Zheng
Tingting Jian
Jian Chen
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2024
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-024-04363-y

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