Related Experiment Video
Updated: Feb 8, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
(Arg)9-SH2 superbinder: a novel promising anticancer therapy to melanoma by blocking phosphotyrosine signaling
An-Dong Liu1, Hui Xu1,2, Ya-Nan Gao1
1Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Background:
Melanoma is a malignant tumor with high misdiagnosis rate and poor prognosis. The bio-targeted therapy is a prevailing method in the treatment of melanoma; however, the accompanying drug resistance is inevitable. SH2 superbinder, a triple-mutant of the Src Homology 2 (SH2) domain, shows potent antitumor ability by replacing natural SH2-containing proteins and blocking multiple pY-based signaling pathways. Polyarginine (Arg)9, a powerful vector for intracellular delivery of large molecules, could transport therapeutic agents across cell membrane. The purpose of this study is to construct (Arg)9-SH2 superbinder and investigate its effects on melanoma cells, expecting to provide potential new approaches for anti-cancer therapy and overcoming the unavoidable drug resistance of single-targeted antitumor agents.
Methods:
(Arg)9 and SH2 superbinder were fused to form (Arg)9-SH2 superbinder via genetic engineering. Pull down assay was performed to identify that (Arg)9-SH2 superbinder could capture a wide variety of pY proteins. Immunofluorescence was used to detect the efficiency of (Arg)9-SH2 superbinder entering cells. The proliferation ability was assessed by MTT and colony formation assay. In addition, wound healing and transwell assay were performed to evaluate migration of B16F10, A375 and A375/DDP cells. Moreover, apoptosis caused by (Arg)9-SH2 superbinder was analyzed by flow cytometry-based Annexin V/PI. Furthermore, western blot revealed that (Arg)9-SH2 superbinder influenced some pY-related signaling pathways. Finally, B16F10 xenograft model was established to confirm whether (Arg)9-SH2 superbinder could restrain the growth of tumor.
Results:
Our data showed that (Arg)9-SH2 superbinder had the ability to enter melanoma cells effectively and displayed strong affinities for various pY proteins. Furthermore, (Arg)9-SH2 superbinder could repress proliferation, migration and induce apoptosis of melanoma cells by regulating PI3K/AKT, MAPK/ERK and JAK/STAT signaling pathways. Importantly, (Arg)9-SH2 superbinder could significantly inhibit the growth of tumor in mice.
Conclusions:
(Arg)9-SH2 superbinder exhibited high affinities for pY proteins, which showed effective anticancer ability by replacing SH2-containing proteins and blocking diverse pY-based pathways. The remarkable ability of (Arg)9-SH2 superbinder to inhibit cancer cell proliferation and tumor growth might open the door to explore the SH2 superbinder as a therapeutic agent for cancer treatment.
Insights
A novel (Arg)9-SH2 superbinder effectively targets melanoma cells, inhibiting proliferation and tumor growth by blocking key signaling pathways. This offers a promising new strategy for cancer therapy and overcoming drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Melanoma presents a significant challenge due to high misdiagnosis rates and poor prognoses.
- Drug resistance is a major limitation in current bio-targeted melanoma therapies.
- SH2 superbinder, a modified Src Homology 2 domain, demonstrates potent anti-tumor capabilities by disrupting pY-based signaling pathways.
Purpose of the Study:
- To construct and evaluate the efficacy of a novel (Arg)9-SH2 superbinder conjugate.
- To investigate the anti-cancer effects of (Arg)9-SH2 superbinder on melanoma cells.
- To explore its potential in overcoming drug resistance in anti-cancer therapies.
Main Methods:
- Genetic engineering was used to create the (Arg)9-SH2 superbinder.
- Cellular uptake, proliferation (MTT, colony formation), migration (wound healing, transwell), and apoptosis (Annexin V/PI) assays were performed.
- Western blot analysis and a B16F10 xenograft model were utilized to assess signaling pathway modulation and in vivo tumor growth inhibition.
Main Results:
- The (Arg)9-SH2 superbinder demonstrated effective cellular entry and strong binding to pY proteins.
- It significantly repressed melanoma cell proliferation and migration while inducing apoptosis.
- The compound regulated key signaling pathways including PI3K/AKT, MAPK/ERK, and JAK/STAT, and inhibited tumor growth in vivo.
Conclusions:
- The (Arg)9-SH2 superbinder exhibits potent anti-cancer activity by targeting diverse pY-based pathways.
- Its ability to inhibit cancer cell proliferation and tumor growth suggests its therapeutic potential.
- This approach may offer new avenues for treating melanoma and overcoming drug resistance.
Related Concept Videos
00:59Gene Therapy
01:22Block Diagram Reduction
The first step in this process is the identification and relocation of a branch point. A branch point, where a...
01:25Elements of Block Diagrams
A block diagram typically includes essential elements such as comparators, blocks, and feedback loops. Each of these elements...
01:26Group Therapy
01:45Endocrine Signaling
01:30Bacterial Signaling