177 results about "Resistant cell" patented technology

The invention discloses a pharmaceutical composition for reversing pancreatic cancer gemcitabine drug resistance and application of the pharmaceutical composition, and belongs to the technical field of biological medicine. The composition comprises a generic FGFR inhibitor delatinib and gemcitabine, the concentration of the delatinib is 25 to 50 mg / kg, and the concentration of the gemcitabine is 20 to 30 mg / kg. By inhibiting an FGFR2 / FGFR3 signal channel and reducing the expression of FGFR protein in drug-resistant cells, the chemosensitivity of gemcitabine is synergistically enhanced, the apoptosis induction rate is increased by more than two times, and the synergic index (CI) is less than 1. In-vitro and nude mouse transplantation tumor experiments prove that the composition can significantly inhibit the proliferation of gemcitabine drug-resistant pancreatic cancer cells. The Gemcitabine drug-resistant pancreatic cancer drug can be used for preparing a drug for treating Gemcitabine drug-resistant pancreatic cancer with high FGFR3 expression, patients are screened through immunohistochemistry or gene sequencing, intravenous injection or oral administration is adopted, dosage forms comprise freeze-dried powder injection, capsules or tablets, and a new strategy is provided for pancreatic cancer drug-resistant treatment.

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

The invention relates to the technical field of cell engineering, and particularly discloses a construction method and application of a sika deer immortalized renal epithelial cell line, and the construction method comprises the following steps: taking renal epithelial primary cells from healthy sika deer renal cortex tissues to obtain primary renal epithelial cells; treating the primary renal epithelial cells with trypsin to obtain a cell suspension; inoculating the cell suspension into a complete culture medium, and transfecting with lentivirus loaded with SV40 large T antigen genes to obtain transfected cells; 3 [mu] g / mL puromycin is applied to the transfected cells for selective culture, so that non-transfected cells are eliminated, and drug-resistant cells are obtained; carrying out continuous passage on the drug-resistant cells for at least 30 generations to obtain the immortalized renal epithelial cell line of the sika deer; according to the invention, through a specific action mechanism (inhibiting a p53 / pRb pathway and blocking cell cycle exit) of the SV40 large T antigen, a proliferation limit caused by inhibition of telomerase activity of primary cells of the cervidae animals is overcome, and a cell resource library capable of realizing continuous passage is established.

The invention provides application of a copper death inducer in preparation of a medicine for treating osimertinib-resistant non-small cell lung cancer, and belongs to the technical field of treatment of non-small cell lung cancer. According to the invention, through high-throughput drug screening, the copper death inducer copper diethyl dithiocarbamate (CuET) and osimertinib are combined for use, so that a remarkable synergistic anti-cancer effect is achieved; furthermore, through detection of a wild type and osimertinib drug-resistant cell line model, an osimertinib sensitive and drug-resistant patient-derived organoid and a mouse xenotransplantation model, it is found that the anti-tumor effect of osimertinib can be remarkably enhanced through copper death induction, and osimertinib drug resistance is overcome. According to the technical scheme provided by the invention, osimertinib drug-resistant non-small cell lung cancer cells can be effectively killed, the curative effect of osimertinib in sensitive and drug-resistant models is remarkably enhanced, and an application scene is provided for copper death in tumor treatment.

The invention relates to the technical field of biology, in particular to a human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 and application thereof.The human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 is preserved in the China Center for Type Culture Collection on May 11, 2023, the preservation number is CCTCC NO: C2023103, the IC50 value of the human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 to gemcitabine is 314.5 mu M, the IC50 value of a parent cell HUCCT1 to gemcitabine is 12.7 mu M, the drug-resistant index is up to 24.8, and the human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 can be used as a drug-resistant cell line. The cell body is obviously enlarged and rounded or is more irregular in shape, the specific volume of the cell cytoplasm is larger, binuclear or multinuclear appears in the cell, and the drug-resistant cell presents obvious bulk aggregation growth; after 24 hours, the growth rate of the HuCCT-1-GEM-2 cell is obviously slower than that of a parent cell, and the HuCCT-1-GEM-2 cell can be used for researching the drug resistance mechanism of bile duct cancer.

The invention provides application of tipirfarb in reversing osimertinib drug resistance, and relates to the technical field of medicines. The research of the inventor finds that the high expression of the MAST1 protein induces the targeted drug resistance of lung cancer, and the MAST1 protein can be used as an anti-drug-resistance action target. A new MAST1 inhibitor tipirfarb is obtained through virtual screening, and the antitumor activity of osimertinib on drug-resistant cells can be enhanced. The invention lays a foundation for subsequent development of an MAST1-targeted anti-drug-resistance strategy, provides brand new anti-drug-resistance targets and candidate molecules for targeted therapy of lung cancer, and has clinical value.

This invention discloses a butyrolactone compound with multidrug resistance reverse transcription activity, its preparation method, and its uses. The compound's structural formula is shown in Figure I. The preparation method includes the following steps: fermenting *Aspergillus pyrolyticus* (accession number CCTCC NO: M2014086) to obtain a butyrolactone fermentation product; extracting the fermentation product with ethyl acetate to obtain a crude extract; degreasing the crude extract with hexane and dichloromethane to obtain a final extract; and purifying the final extract using normal-phase silica gel column chromatography, reversed-phase medium-pressure column chromatography, and reversed-phase semi-preparative high-performance liquid chromatography. The advantage of this butyrolactone compound is that it possesses multidrug resistance reverse transcription activity and the ability to regulate P-gp-mediated drug efflux in multidrug-resistant cell lines, making it a potential drug for treating multidrug-resistant cancers.

The invention relates to application of SMARCC1 in preparation of a medicine for treating carfilzomib-resistant multiple myeloma, and belongs to the technical field of biological medicine. According to the invention, direct association between SMARCC1 and the drug resistance of multiple myeloma to carfilzomib is determined for the first time, and the sensitivity of drug-resistant cells to carfilzomib can be significantly enhanced by down-regulating the expression of the gene. Specifically, through systematic analysis on clinical data, SMARCC1 is found to be remarkably and highly expressed in relapse / refractory MM patients and is closely related to poor survival. The SMARCC1 knock-down obviously inhibits the multiplication capacity of multiple myeloma drug-resistant cells, so that the SMARCC1 not only promotes the multiplication capacity of the drug-resistant cells, but also is closely related to the drug resistance of the multiple myeloma cells to carfilzomib, which prompts that the SMARCC1 can be used as a potential therapeutic target and is used for reversing the carfilzomib drug resistance of multiple myeloma.

The application discloses application of Ophisaurus apodus in preparation of a drug for reversing drug resistance of gastric cancer and belongs to the technical field of medicines. The application can reduce tumor volume and size, promote drug resistance cell apoptosis, and reverse the chemotherapeutic drug resistance of a nude mouse with gastric cancer by jointly using Ophisaurus apodus in different parts of the body and cisplatin, by down-regulating P-gp, MRP1 and Bcl-2 protein expression, and by up-regulating Bax protein expression. The effect of the tail + cisplatin group is the most significant.

The invention relates to application of a KRT7-AS inhibitor in preparation of a medicine for treating ovarian cancer or paclitaxel drug resistance of the ovarian cancer. The invention discloses a mechanism of KRT7-AS for promoting ovarian cancer progression by inhibiting ferroptosis for the first time. After KRT7-AS is knocked down by utilizing an shRNA (short hairpin ribonucleic acid) inhibition technology, biological behaviors of ovarian cancer cells and ovarian cancer paclitaxel drug-resistant cells are influenced: proliferation, migration and invasion capabilities are reduced to different degrees, and meanwhile, ferroptosis is activated to inhibit tumor growth. The invention provides a new thought and a potential target for precise treatment of ovarian cancer, and is expected to bring good news to ovarian cancer patients. Long-chain non-coding RNA KRT7-AS is novel carcinogenic lncRNA of ovarian cancer, and the effect of KRT7-AS knockout in the ovarian cancer cell process is researched. By targeting KRT7-AS, ferroptosis of ovarian cancer cells is regulated and controlled, so that tumor progression is influenced. The KRT7-AS inhibitor is used for targeting KRT7-AS, can be used as a treatment method for treating ovarian cancer, and is an innovative strategy for treating ovarian cancer.

This invention relates to drug-resistant breast cancer cells and their applications, belonging to the field of tumor cell technology. The drug-resistant breast cancer cells of this invention are human mammary ductal carcinoma cells T47DR and / or human breast cancer cells MCF7R. The human mammary ductal carcinoma cells T47DR were deposited at the Guangdong Provincial Microbial Culture Collection Center on October 25, 2024, with accession number GDMCC No: 65348; the human breast cancer cells MCF7R were deposited at the same center on October 25, 2024, with accession number GDMCC No: 65347. This invention demonstrates that the clonogenic ability, migration ability, anti-apoptotic ability, and spheroidization ability of drug-resistant breast cancer cells are significantly enhanced. They can form tumors independently of estrogen and metastasize throughout the body in a short period of time. The tumor stemness of the drug-resistant cells is enhanced, and they exhibit resistance to apelexifen and / or tamoxifen.

The invention discloses an application of MetAP2 as a target spot in a drug for reducing drug resistance of multiple myeloma cells. According to the invention, expression of mRNA and protein of MetAP2 in MM drug-resistant cells is increased; when the protein expression of MetAP2 in the MM cells is exogenously changed, the sensitivity of the MM cells to BTZ can be changed; the lifetime of a myeloma mouse model established by using the MM cell for knocking down the MetAP2 is obviously prolonged, and the bone destruction condition is effectively improved. The invention provides a new solution thought for clinically inhibiting tumor growth and improving drug resistance of multiple myeloma, and has important clinical significance and transformation value.

A method for identifying a protein associated with a receptor-ligand interaction is described. The method comprises providing a population of engineered cells comprising a targeting library targeting specific gene expression, contacting the population of cells with a recombinant toxin fusion for sufficient time, and identifying proteins in the selection pool of cells by sequencing one or more of the nucleic acid molecule comprised in the selection pool of cells, thereby identifying the target gene. Toxin-resistant cell lines, toxin-producing cell lines, recombinant toxin fusions, probes and methods producing same, and kits thereof, are also provided.

The invention belongs to the technical field of biological medicine, and particularly relates to application of an anti-HIV drug in inhibition of non-small cell lung cancer drug resistance. The invention finds that the combined use of the anti-HIV drug and EGFR-TKI can effectively and specifically target the MRD drug-resistant cells, inhibit the formation of the MRD drug-resistant cells, significantly improve the curative effect of EGFR-TKI and delay tumor recurrence.

Embodiments disclosed herein use forward genetics tools (e.g., ORF libraries, perturbation libraries) to study fitness advantages under immune pressure, including resistance mechanisms. Once the resistance mechanisms are identified, vulnerabilities (i.e., dependencies) in resistant cells can be identified (e.g., synthetic lethality screens in resistant cancer cells). For example, drug or CRISPR screening can be performed in cells with an identified resistant state. Embodiments disclosed herein also provide targets for resistance to IFN-y treatment.

The invention relates to application of an HOXB9 inhibitor in a medicine for reversing oxaliplatin resistance of gastric cancer, and belongs to the field of biological medicine. The invention discloses for the first time: HOXB9 is remarkably high in expression and is positively correlated with poor prognosis in tissues of patients with gastric cancer, which are poor in curative effect after chemotherapy containing oxaliplatin; by constructing an oxaliplatin drug-resistant gastric cancer cell strain and a patient-derived organ model, the HOXB9 is proved to specifically mediate the survival of the drug-resistant cell strain by activating a focal adhesion signaling pathway (p-FAK / AKT), and the HOXB9 is irrelevant to cell proliferation. Aiming at the mechanism, shRNA nucleic acid molecules (SEQ ID NO: 1-2) targeting HOXB9 are provided, and drug-resistant cell strains can be selectively killed through lentiviral vector delivery, so that the drug-resistant cell IC50 is reduced by more than 50%, the apoptosis rate is increased by 3 times, and the chemotherapy resistance of organoids is reversed. The invention provides a brand-new target spot and a treatment scheme for overcoming the drug resistance of oxaliplatin for gastric cancer.

The invention discloses a 2-amino-4-anilino pyrimidine compound as well as a preparation method and application of the 2-amino-4-anilino pyrimidine compound. The compound has a strong inhibition effect on EGFR (epidermal growth factor receptor) gene mutation targets and c-MET and has a strong inhibition effect on osimertinib drug-resistant cells; and the compound can inhibit proliferation of various tumor cells, and provides excellent application prospects for treatment of EGFR gene mutation and MET amplified malignant tumors.

The invention relates to application of a proteasome inhibitor in preparation of a medicine for treating tumors resistant to a tyrosine kinase inhibitor, and in the application, a plurality of strains of liver cancer cells with drug resistance to lenvatinib or regorafenib are constructed by utilizing a plurality of human liver cancer cell lines with different genetic backgrounds; a high-throughput CRISPR (clustered regularly interspaced short palindromic repeats) gene knockout screening technology and a patent medicine gene CRISPR library are utilized, and gene targets of which the gene knockout or inactivation can better kill drug-resistant cells are specifically identified from thousands of patent medicine genes. Wherein the function inactivation of a plurality of genes in the proteasome family shows more obvious cell killing activity in a plurality of drug-resistant cell models compared with non-drug-resistant cells. The invention discovers and verifies that the proteasome inhibitor has a specific killing effect on tyrosine kinase inhibitor drug-resistant liver cancer for the first time.

The present disclosure relates generally to lipid nanoparticles (LNPs) and compositions comprising the same, and their use for delivering agents, such as nucleic acid-based therapeutic agents, particularly to transfected resistant cells and / or lung tissue.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an HS2ST1 inhibitor in preparation of a medicine for treating KRAS inhibitor drug-resistant tumors. At present, more than 50% of KRAS inhibitor drug-resistant patients have unclear mechanisms and lack of effective intervention targets, and HS2ST1 is identified as a key regulation target of KRAS inhibitor drug resistance for the first time. Researches find that the expression of HS2ST1 in KRAS inhibitor drug-resistant cells is significantly up-regulated; functional experiments prove that targeted intervention of the HS2ST1 can effectively enhance the curative effect of the KRAS inhibitor and reverse the drug resistance phenotype of the KRAS inhibitor, and a new strategy and a potential treatment direction are provided for overcoming KRAS targeted treatment drug resistance.

The application discloses application of AGPG in treatment of endocrine-resistant estrogen receptor positive breast cancer, and finds that AGPG can promote in-vitro endocrine-resistant cell cycle progression and cell proliferation through stable knockout research. Finally, a small interfering RNA drug is tested in an in-vivo experiment, and it is further proved that down-regulation of AGPG mediated by the small interfering RNA can significantly inhibit growth of tamoxifen-resistant MCF7 xenografts.

The invention belongs to the technical field of medicines, and relates to a bibenzyl polycyclic compound, a preparation method thereof and application of the bibenzyl polycyclic compound in preparation of anti-tumor disease medicines. The chemical structure is shown as a formula A. In the formula, X and Y are independently selected from C or N respectively; in the formula (I), R1 is absent,-H,-CH3,-C2H5,-OCH3,-OBn,-F,-Br,-NH2,-OH,-NHCH3,-CN or-CONH2; r < 2 >, R < 3 >, R < 4 >, R < 5 > and R < 6 > are respectively and independently selected from-H,-CH3,-C2H5,-OCH3,-OBn,-F,-Br,-NH2,-OH,-NHCH3,-CN and-CONH2; r7 is-H or, and n is 1 or 2. The compound provided by the invention has a good inhibition effect on various cancer cells, has selectivity on drug-resistant cells, has small toxicity on normal cells, and can be used as a novel potential anti-tumor drug.

The application discloses application of cryptoxanthin in preparation of a combination drug for treating lenalidomide-resistant multiple myeloma, and relates to the technical field of medicines.The application verifies the effect and potential mechanism of betaCRY in treating LEN-resistant MM through in-vivo and in-vitro experiments, specifically, betaCRY can inhibit the expression level of FSP1 protein in LEN-resistant tumors, thereby inducing the occurrence of ferroptosis, and then significantly reducing the activity of LEN-resistant tumor cells, and finally achieving the purpose of overcoming LEN tumor drug resistance.The discovery in the application proves that a plant extract serves as a new FSP1 inhibitor in the treatment of LEN-resistant MM cells, and provides a theoretical basis for further using betaCRY to treat LEN-resistant MM in clinic.Therefore, the application has a good application prospect in the field of treating drug-resistant MM.

The invention discloses an application of PINK1 in regulation and control of ER positive breast cancer tamoxifen drug resistance. The invention relates to application of PINK1 as a biomarker in evaluating the tamoxifen resistance of ER positive breast cancer cells. The drug resistance is evaluated by detecting the expression level of PINK1 in a sample and combining mitochondrial autophagy activity. The expression level of the PINK1 comprises an mRNA level and / or a protein level. According to the invention, the drug resistance formation process is systematically analyzed from the perspective of quality control of an organelle of mitochondrial autophagy, and through public database analysis and experimental verification, the overall up-regulation of the mitochondrial autophagy pathway in drug-resistant cells is clearly revealed, and the drug-resistant phenotype is promoted by maintaining the mitochondrial steady state, thereby opening up a new direction for understanding the drug-resistant mechanism.

The invention discloses a PROTAC compound for targeted degradation of ER and application of the PROTAC compound, and belongs to the technical field of medicines. A novel ERalpha PROTAC molecule is designed and synthesized, specific degradation of ERalpha is realized by utilizing a PROTAC technology, and the ERalpha-PROTAC molecule shows excellent anti-tumor activity in ERalpha positive breast cancer cells, also has a remarkable inhibition effect on drug-resistant cells, is excellent in pharmacokinetic property, high in bioavailability and remarkable in-vivo drug effect, and can be used for preparing ERalpha-PROTAC molecules. The polypeptide has the potential of being developed into a novel breast cancer treatment medicine.

The invention discloses a formamide pyrazole compound as well as a pharmaceutical composition and application thereof. The compound has a structure as shown in a formula (I), has relatively strong anti-proliferative activity on a TRK xDFG mutation drug-resistant cell strain Ba / F3-LMNA-NTRK1-G667C, can effectively down-regulate the TRKAG667C protein level in a Ba / F3-LMNA-NTRK1-G667C cell, has an application value as a TRK degradation agent, is used for preparing an anti-tumor drug, and particularly provides a new drug molecule for treating mutation drug-resistant cancers.

The application discloses a butyl tin-cycloiridium phenanthroline complex with an aggregation-induced emission (AIE) property, a preparation method of the complex and anticancer application of the complex. The structural formula of the complex is shown as formula (I), and R is one of hydrogen, a phenyl group, a p-tolyl group, a p-bromophenyl group, a p-fluorophenyl group, a biphenyl group, a triphenylamine group, a carbazole group, a tetraphenyl ethene group and a triphenylbenzene group. The growth inhibition rates of the target compound on human alveolar basal epithelial carcinoma cells (A549) and cisplatin-resistant cells (A549 / DDP), cervical cancer cells (Hela) and human lung normal epithelial cells (BEAS-2B) are tested, and it is found through comparison that the target compound shows potential anticancer activity. In addition, the target compound shows unique AIE emission characteristics. The target compound mainly targets the lysosomes of A549 cells, and influences the mitochondria to cause the decline of the mitochondrial membrane potential, thereby showing anticancer activity.

The invention discloses a gold (I) complex containing an alkyne ligand, a preparation method of the gold (I) complex and application of the gold (I) complex in preparation of antitumor drugs, the gold (I) complex has a structure as shown in a general formula I, a phosphorus ligand is selected from diphenyl-2-pyridine phosphine or tricyclohexylphosphine, and Rx is an organic group selected from a specific alkyne ligand; according to the preparation method, chloroauric acid is taken as an initial raw material, sequentially reacts with dimethyl sulfide and an organic phosphine ligand, and finally is coupled with an alkyne ligand under an alkaline condition, so that the steps are simple and convenient, the conditions are mild, and the yield is high; in-vitro activity experiments show that the complex shows remarkable proliferation inhibition activity on ovarian cancer, malignant melanoma, non-small cell lung cancer and cisplatin-resistant cell strains thereof, the effect of the complex is superior to that of cisplatin and auronafine, and a candidate compound is provided for developing a novel targeted anti-tumor drug for overcoming the drug resistance of platinum drugs.

The invention discloses an alpha2delta1 targeted degradation molecule alpha2delta1-LYTAC as well as a derivative and application thereof. The alpha2delta1 targeted degradation molecule alpha2delta1-LYTAC comprises an alpha2delta1 antagonistic polypeptide with an amino acid sequence as shown in SEQ ID No: 1 and a medicine. The alpha2delta1-LYTAC can be combined with alpha2delta1, the alpha2delta1 protein is degraded by combining with the alpha2delta1, and a downstream signal channel of the alpha2delta1 protein is blocked, so that liver cancer cell proliferation is inhibited, liver cancer cell apoptosis is promoted, especially tumor drug-resistant cells are promoted, effective small molecule drugs for treating liver cancer and the like are provided, and the alpha2delta1-LYTAC can be widely applied to the fields of medicine and biology.

The invention relates to the technical field of cell engineering, in particular to a lobaplatin drug-resistant cell strain for triple negative breast cancer, the cell strain is named as the lobaplatin drug-resistant cell strain SUM-159PT-LBP for triple negative breast cancer, the cell strain is preserved in China Center for Type Culture Collection (CCTCC) on May 7, 2025, and the preservation number is CCTCC NO: C2025150; the drug-resistant cell strain provided by the invention is constructed by adopting a lobaplatin concentration gradual increase method for induction and intermittent maintenance culture, and finally can stably grow and pass in a lobaplatin culture system with the action concentration of 5 mu M, and the drug-resistant index (RI) is 5.72. Besides, the drug-resistant cell strain can also be used for analyzing the biological phenotype and the drug-resistant mechanism of the triple negative breast cancer after drug resistance, screening drug-resistant markers and finding potential antitumor drugs, and has a scientific research transformation effect and a clinical application prospect.