Biomaterial Database

Tanshinone I attenuates proliferation and chemoresistance of cervical cancer in a KRAS-dependent manner. 2019

Sidi Dun, and Lan Gao

Department of Gynaecology and Obstetrics, Daqing Oilfield General Hospital, Daqing, China.

Chemoresistance is a common occurrence during advanced or recurrent cervical cancer therapy when treated by conventional treatment, platinum-based chemotherapy. This study aimed to investigate the effect and underlying mechanism of tanshinone I on attenuating proliferation and chemoresistance of cervical cancer cells. In cervical cancer cells, cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell count, and soft-agar colony-formation assay. rVista analysis and luciferase reporter assay were used to explore the upstream regulator of KRAS, and the expression levels of key genes were also detected. Western blot analysis showed that tanshinone I significantly suppressed KRAS expression and inhibited AKT phosphorylation. rVista analysis and luciferase reporter assay demonstrated that ELK1 can binds directly to KRAS promoter and positively regulates KRAS expression. MTT assay showed that KRAS or ELK1 overexpression significantly attenuated the suppressive effects of tanshinone I on HeLa cells proliferation. In addition, tanshinone I recovered the cisplatin sensitivity of HeLa CR cells, whereas KRAS or ELK1 overexpression significantly inhibited this phenomenon. Our results suggested that tanshinone I had anticancer effects on cervical cancer cells via inhibiting ELK1 and downregulating KRAS-AKT axis, which subsequently suppressed the proliferation and cisplatin resistance of cervical cancer cells.

UI	MeSH Term	Description	Entries
D011905	Genes, ras	Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.	Ha-ras Genes,Ki-ras Genes,N-ras Genes,c-Ha-ras Genes,c-Ki-ras Genes,c-N-ras Genes,ras Genes,v-Ha-ras Genes,v-Ki-ras Genes,H-ras Genes,H-ras Oncogenes,Ha-ras Oncogenes,K-ras Genes,K-ras Oncogenes,Ki-ras Oncogenes,N-ras Oncogenes,c-H-ras Genes,c-H-ras Proto-Oncogenes,c-Ha-ras Proto-Oncogenes,c-K-ras Genes,c-K-ras Proto-Oncogenes,c-Ki-ras Proto-Oncogenes,c-N-ras Proto-Oncogenes,ras Oncogene,v-H-ras Genes,v-H-ras Oncogenes,v-Ha-ras Oncogenes,v-K-ras Genes,v-K-ras Oncogenes,v-Ki-ras Oncogenes,Gene, Ha-ras,Gene, Ki-ras,Gene, v-Ha-ras,Gene, v-Ki-ras,Genes, Ha-ras,Genes, Ki-ras,Genes, N-ras,Genes, v-Ha-ras,Genes, v-Ki-ras,H ras Genes,H ras Oncogenes,H-ras Gene,H-ras Oncogene,Ha ras Genes,Ha ras Oncogenes,Ha-ras Gene,Ha-ras Oncogene,K ras Genes,K ras Oncogenes,K-ras Gene,K-ras Oncogene,Ki ras Genes,Ki ras Oncogenes,Ki-ras Gene,Ki-ras Oncogene,N ras Genes,N ras Oncogenes,N-ras Gene,N-ras Oncogene,c H ras Genes,c H ras Proto Oncogenes,c Ha ras Genes,c Ha ras Proto Oncogenes,c K ras Genes,c K ras Proto Oncogenes,c Ki ras Genes,c Ki ras Proto Oncogenes,c N ras Genes,c N ras Proto Oncogenes,c-H-ras Gene,c-H-ras Proto-Oncogene,c-Ha-ras Gene,c-Ha-ras Proto-Oncogene,c-K-ras Gene,c-K-ras Proto-Oncogene,c-Ki-ras Gene,c-Ki-ras Proto-Oncogene,c-N-ras Gene,c-N-ras Proto-Oncogene,ras Gene,ras Oncogenes,v H ras Genes,v H ras Oncogenes,v Ha ras Genes,v Ha ras Oncogenes,v K ras Genes,v K ras Oncogenes,v Ki ras Genes,v Ki ras Oncogenes,v-H-ras Gene,v-H-ras Oncogene,v-Ha-ras Gene,v-Ha-ras Oncogene,v-K-ras Gene,v-K-ras Oncogene,v-Ki-ras Gene,v-Ki-ras Oncogene
D002583	Uterine Cervical Neoplasms	Tumors or cancer of the UTERINE CERVIX.	Cancer of Cervix,Cancer of the Cervix,Cancer of the Uterine Cervix,Cervical Cancer,Cervical Neoplasms,Cervix Cancer,Cervix Neoplasms,Neoplasms, Cervical,Neoplasms, Cervix,Uterine Cervical Cancer,Cancer, Cervical,Cancer, Cervix,Cancer, Uterine Cervical,Cervical Cancer, Uterine,Cervical Cancers,Cervical Neoplasm,Cervical Neoplasm, Uterine,Cervix Neoplasm,Neoplasm, Cervix,Neoplasm, Uterine Cervical,Uterine Cervical Cancers,Uterine Cervical Neoplasm
D005260	Female		Females
D006367	HeLa Cells	The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.	Cell, HeLa,Cells, HeLa,HeLa Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015153	Blotting, Western	Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.	Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D016133	Polymerase Chain Reaction	In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.	Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D045784	Abietanes	A subclass of cyclical DITERPENES that contain the abietane ring structure.	Abietane Diterpene,Abietane Diterpenoid,Abietane Diterpenoids,Diterpenes, Abietane,Isopimarane,Isopimaranes,Totarane Diterpene,Totarane Diterpenes,Totaranes,Diterpenes, Pimarane,Pimaranes,Abietane Diterpenes,Diterpene, Abietane,Diterpene, Totarane,Diterpenoid, Abietane,Pimarane Diterpenes
D049109	Cell Proliferation	All of the processes involved in increasing CELL NUMBER including CELL DIVISION.	Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D050807	ets-Domain Protein Elk-1	A member of the ternary complex family of ets-related transcription factors that is regulated by MITOGEN-ACTIVATED PROTEIN KINASES including JNK MITOGEN-ACTIVATED PROTEIN KINASES; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; and P38 MITOGEN-ACTIVATED PROTEIN KINASES.	Elk-1 ets-Domain Protein,Elk-1 Transcription Factor,Elk1 Transcription Factor,Elk1 ets-Domain Protein,Ets-Like Protein 1,Transcription Factor Elk1,Elk 1 Transcription Factor,Elk 1 ets Domain Protein,Elk-1, ets-Domain Protein,Elk1 ets Domain Protein,Elk1, Transcription Factor,Ets Like Protein 1,Factor Elk1, Transcription,Transcription Factor, Elk-1,Transcription Factor, Elk1,ets Domain Protein Elk 1,ets-Domain Protein, Elk-1,ets-Domain Protein, Elk1