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Pharmaceutical composition containing mTOR inhibitor and application thereof

A composition and inhibitor technology, applied in the field of tumor treatment, can solve the problems of single treatment plan, poor treatment effect and poor prognosis for penile cancer, and achieve the effects of improving single treatment plan, improving prognosis and expanding drug spectrum

Pending Publication Date: 2021-07-09
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of the above-mentioned problems and deficiencies, the present invention provides a pharmaceutical composition containing an mTOR inhibitor to solve the problems of single treatment scheme, poor treatment effect, and poor prognosis in the prior art for penile cancer, thereby effectively broadening the drug spectrum of penile cancer , improve its therapeutic effect, and provide a new theoretical basis and experimental basis for the clinical medication and treatment of penile cancer

Method used

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  • Pharmaceutical composition containing mTOR inhibitor and application thereof
  • Pharmaceutical composition containing mTOR inhibitor and application thereof
  • Pharmaceutical composition containing mTOR inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Cell Proliferation Inhibition Experiment in Vitro

[0038] (1) Take Penl-1, Penl-2, 149RCa, 149RM and LM156 cells in the logarithmic growth phase and inoculate them in a 96-well plate at a certain density (3000-5000 / well);

[0039] (2) After 24 hours, the old medium was discarded, and the cells were treated with medium containing different concentrations of drugs; the drugs used were AZD-8055, Rapamycin, Everolimus, Temsirolimus, Paclitaxel (Taxol) and cisplatin ( DDP), drug concentration gradients were 100 μM, 20 μM, 4 μM, 0.8 μM, 0.16 μM, 0.032 μM, 0.0064 μM, 0.00128 μM and 0 μM, and group 10 was the blank group without inoculating cells;

[0040] (3) After culturing for 48 hours, add 20 μL of 5 mg / mL MTT solution to each well, place in a 37°C incubator and incubate in the dark for 4 hours, discard the medium carefully, try not to absorb the formazan at the bottom of the well, and add DMSO to dissolve the formazan. Zan was dissolved, placed on a shaker and ...

Embodiment 2

[0047] Example 2 Penl-2 anti-tumor experiment in vivo

[0048] To further confirm the effect of mTOR inhibitors in penile cancer, rapamycin was chosen as an example to verify its anti-tumor effect in vivo.

[0049] Male nude mice aged about 4-6 weeks were selected to carry out the Penl-2 cell subcutaneous xenograft tumor growth inhibition experiment, and the specific experimental method was as follows:

[0050] (1) Culture Penl-2 cells in vitro, collect cells in logarithmic growth phase, digest, centrifuge, and resuspend in PBS;

[0051] (2) Put 4×10 6 The cells were inoculated subcutaneously in the right scapula of two nude mice, and after the tumors formed, the tumors were taken out and evenly divided into volumes of about 5 mm. 3 Tumor mass of size;

[0052] (3) The obtained tumor mass was retransplanted subcutaneously into several new nude mice. After the tumors formed, 21 nude mice were randomly divided into 3 groups, with 7 mice in each group, and administered by intr...

Embodiment 3149

[0056] Example 3 149RCa in vivo anti-tumor experiment

[0057] In order to further confirm the inhibitory effect of mTOR inhibitors on penile cancer in vivo, the 149RCa cell line was further selected for the construction of tumor models in vivo. Simultaneous experiments with Lapatinib, Afatinib, Carfilzomib and Osimertinib (AZD-9291) to fully verify and compare mTOR inhibitors against penile cancer in vivo Effect and inhibitory effect compared with other antitumor drugs.

[0058] Male nude mice aged about 4-6 weeks were selected to carry out the growth inhibition experiment of 149RCa cell subcutaneous xenograft tumor, and the specific experimental method was as follows:

[0059] (1) Culture 149RCa cells in vitro, collect cells in logarithmic growth phase, digest, centrifuge, and resuspend in PBS;

[0060] (2) Put 4×10 6 The cells were inoculated into the subcutaneous area of ​​the right shoulder blade of 3 nude mice. After tumors formed, the tumors were taken out and evenly...

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Abstract

The invention provides a pharmaceutical composition for treating cancer, especially penis cancer. The pharmaceutical composition comprises an mTOR inhibitor. A large number of long-term studies find that the mTOR pathway inhibitor can generate a remarkable growth inhibition effect on penis cancer cells in vivo and in vitro, while as a contrast, a platinum-containing chemotherapy regimen (cis-platinum and paclitaxel) which is clinically used at present does not show a clear treatment effect in an experiment process, and therefore, the function and potential value of the mTOR inhibitor in the aspect of treating the penile cancer are determined. The invention provides a novel targeted therapeutic scheme for the penile cancer, especially advanced penile cancer, can effectively expand the medication spectrum of the penile cancer, and improves the current situation that the penile cancer therapeutic scheme is single. The pharmaceutical composition plays an important role in improving the prognosis of the penile cancer, and has very important clinical significance and social significance.

Description

technical field [0001] The invention belongs to the technical field of tumor treatment, and in particular relates to a pharmaceutical composition containing an mTOR inhibitor and an application thereof. Background technique [0002] Penile cancer is a rare male malignancy worldwide. The prognosis of penile cancer is closely related to its metastasis status. For early / locally advanced penile cancer, surgery alone / neoadjuvant chemotherapy + surgery can often achieve better curative effect, but for advanced penile cancer, especially patients with distant metastasis , with a very poor prognosis. At present, for metastatic penile cancer, the first-line treatment regimen approved by the NCCN guidelines is only TIP (paclitaxel + ifosfamide + cisplatin), and the second-line treatment regimens include PD-1 antibody pembrolizumab and EGFR antibody cetuximab monoclonal antibody. It can be seen that the systemic treatment plan for penile cancer is relatively simple, especially in the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/436A61P35/00A61P35/02A61P15/00
CPCA61K45/06A61K31/436A61P35/00A61P35/02A61P15/00
Inventor 刘然义岳欣刘听雨晏如韩辉
Owner SUN YAT SEN UNIV CANCER CENT
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