TABLE 3.
The main biological processes of cancer progression and embryo implantation, and the targets of related components in traditional Chinese medicine.
| Cell biological processes | The significance in embryonic development | The significance in cancer progression | The related genes obtained in this study | Components of KTHs |
|---|---|---|---|---|
| Regulation of epithelial cell proliferation | Promote the uterus into the receptive state, decidualization of uterine stromal cells and the occurrence of placenta (Zhu et al., 2019) | It can make tumor proliferate rapidly, compress tissue, and promote angiogenesis (Zhong et al., 2020) | AR, TNF, XDH, PPARG, PGR, VDR, STAT3, JUN, MTOR, EGFR, KDR, AKT1, SHH, ITGB3, SCN5A, HIF1A, AGTR1, ITGA4, GLUL, FLT1, FGFR1, TEK, FLT4, WNT3A, and CCND1 | (a), (b), (d), €, and (f) |
| Epithelial cell migration | It can promote the mutual recognition and interaction between blastotrophoblast cells and endometrial cells, and promote the balance of maternal–fetal interface (Zhu et al., 2019) | Cell migration plays an important role in the early occurrence and development of various cancers, especially before primary tumor cells develop into invasive lesions (Hsieh and Wu, 2020) | PTGS2, TNF, PPARG, PTPN11, JUN, MTOR, PIK3CA, SRC, KDR, MMP9, MET, AKT1, ITGB3, HIF1A, ITGB1, GLUL, ABL1, FGFR1, TEK, FLT4, and KIT | (b), (e), and (f) |
| Regulation of tissue remodeling | Embryo implantation and development involve degradation and remodeling of extracellular matrix, placental villous vasculogenesis, and reconstruction of uterine spiral artery (Zhang et al., 2021) | Tumor destroys normal tissue and makes it remodel to change its original biological function (Zhong et al., 2020) | PLG, IL2, VDR, MDM2, MMP2, MMP14, EGFR, SRC, ITGB3, HIF1A, ADRB2, ACE, IL6, and FLT4 | (a), (d), and (e) |
| Response to oxidative stress | Excessive ROS can cause mitochondrial damage, DNA damage, lipid peroxidation, and even cell apoptosis in embryos, and then lead to embryonic development arrest (Ivanov et al., 2021) | High level and long-term oxidative stress can directly damage tissues through this redox system, and also lead to oxidative modification of amino acid residues and DNA mutation, thus promoting the occurrence of tumor (Shrivastava et al., 2021) | PTGS2, TNF, PTGS1, MDM2, JUN, MMP3, MMP2, MMP14, EGFR, MPO, SRC, CDK1, MMP9, MET, AKT1, MAPT, PARP1, HIF1A, JAK2, CASP3, IL6, ABL1, CCNA2, MAPK1, and PSEN1 | (a), (b), (c), (e), and (f) |
| Regulation of mitochondrion organization | In the process of embryo implantation, the number, distribution, and activity of mitochondria are regulated strictly and orderly, and affect the embryo implantation potential at the same time (Moher et al., 2009) | The malignant phenotypes of tumor cells, such as unlimited proliferation, abnormal metabolism, inhibition of apoptosis, strong invasion, and easy metastasis, are also closely related to mitochondrial dysfunction (Roth et al., 2020; Suldina et al., 2018) | BCL2L1, KDR, MMP9, AKT1, MAPT, HIF1A, GBA, and CASP8 | (a), (e), and (f) |
| Response to lipopolysaccharides | Inflammation and infection result in LPS affecting decidual differentiation through toll-like receptor 4, which leads to stress injury and thrombosis of trophoblast (Guo et al., 2019) | LPS can promote tumor survival by activating upregulated inflammatory signaling pathway, and can also increase the expression of adhesion factors of tumor cells to endothelial cells by activating neutrophils (Shetab et al., 2019) | NOS2, PTGS2, TNF, CNR1, MPO, SRC, AKT1, CCR5, REN, JAK2, ELANE, SELE, SELP, CASP3, CASP8, CASP1, IL6, CDK4, ALPL, ABL1, COMT, and MAPK1 | (a), (b), (e), and (f) |
| Regulation of autophagy | Autophagy can affect embryo delayed implantation, abnormal decidua, and reduce the expression of autophagy in endometrial receptive period to ensure the success of embryo implantation (Su et al., 2020) | Moderate autophagy can make the damaged tumor cells survive, while excessive autophagy can accelerate the death of tumor cells (Wang et al., 2019) | STAT3, MTOR, PIK3CA, KDR, MET, AKT1, MAPT, HIF1A, GBA, ADRB2, CASP3, and ABL1 | (a), (b), (e), and (f) |
| Regulation of apoptotic signaling pathway | Proapoptotic factors and antiapoptotic factors play a key role in regulating the survival and apoptosis of embryonic cells, and the balance between them determines the survival or death of embryos (Zhang et al., 2021) | Imbalance in the ratio of proliferation and apoptosis of tumor cells is the key factor in tumorigenesis and progression (Mohamed et al., 2017) | AR, PTGS2, TNF, TERT, MDM2, BCL2L1, SRC, MMP9, AKT1, PARP1, HIF1A, JAK2, CASP8, RET, FGFR1, and PSEN1 | (a), (b), (c), (d), (e), and (f) |
| Regulation of inflammatory response | The balance of pro-inflammatory factors and anti-inflammatory factors promotes endometrial receptivity, and appropriate inflammatory environment promotes embryo implantation and pregnancy maintenance (Quirke et al., 2021) | The infiltration of inflammatory cells and the production of ROS are necessary and sufficient conditions to accelerate the carcinogenesis (Rossi et al., 2021) | NOS2, PTGS2, TNF, IL2, ESR1, CYP19A1, PPARG, CNR1, F2, TLR9, STAT3, MMP3, EGFR, MMP9, GBA, JAK2, ELANE, SELE, CASP1, AGTR1, IL6, and TEK | (a), (b), (e), and (f) |
| Regulation of angiogenesis | On the basis of the original blood vessels, the formation of blood vessels through the process of endothelial cell proliferation, and migration is conducive to the development and infiltration of embryonic cells (Barrientos et al., 2013) | It can promote the secretion of tumor cells, promote angiogenic factors, promote the proliferation of endothelial cells, and chemotaxis the migration of endothelial cells (Li et al., 2019) | PTGS2, TNF, TERT, PPARG, STAT3, KDR, HIF1A, ITGB1, AGTR1, IL6, GLUL, FLT1, ABL1, and TEK | (b), (e), and (f) |
| Epithelial–mesenchymal transition, EMT | It can make endometrial epithelial and stromal cells more invasive and mobile, promote embryonic organ formation, embryonic differentiation, and nervous system differentiation (Ran et al., 2020) | EMT plays an important role in the invasion and metastasis of tumor in situ and the formation of new metastasis. It is an important way of invasion and metastasis of epithelial cell carcinoma, which accounts for more than 90% of malignant tumors in adults (Thiery, 2002) | MMP2, MMP7, NOS2, MET, CDK1, CYP19A1, SHH, JAK2, CCNA2, MMP1, MMP3, MDM2, EGFR, ABL1, CHEK2, PGR, RET, ABCB1, STAT3, IL6, CASP3, VDR, ABCG2, PIK3CA, IGF1R, HIF1A, TLR9, JUN, AR, TNF, ITGB1, KIT, F2, PTGS2, CCND1, ESR1, CDK4, SLC2A1, FLT1, TERT, SRC, REN, PTPN11, ALK, CASP8, PPARG, NR3C1, MTOR, DRD2, AGTR1, HSP90AA1, PARP1, KDR, BCL2L1, and MMP9 | (a), (b), (c), (d), (e), and (f) |
Note. The main active components in KTHs: (a) Sophranol; (b) Japonine; (c) Matrine; (d) Lysine; (e) Sylvestroside III; and (f) Gentisin.