RESUMEN
Ginger (Zingiber officinale Roscoe), a widely consumed edible and medicinal plant, possesses significant nutritional and economic value. Abiotic stresses such as drought and low temperatures can impact the growth and development of ginger. The plant-specific transcription factor Teosinte branched1/cycloidea/proliferating cell factor (TCP) has progressively been identified in various plants for its role in regulating plant growth and development as well as conferring resistance to abiotic stresses. However, limited information on the TCP family is available in ginger. In this study, we identified 20 TCP members in the ginger genome, which were randomly distributed across 9 chromosomes. Based on phylogenetic analysis, these ginger TCP were classified into two subfamilies: Class I (PCF) and Class II (CIN, CYC/TB). The classification of the identified ginger TCPs was supported by a multi-species phylogenetic tree and motif structure analysis, suggesting that the amplification of the ginger TCP gene family occurred prior to the differentiation of angiosperms. The promoter region of ginger TCP genes was found to contain numerous cis-acting elements associated with plant growth, development, and abiotic stress response. Among these elements, the stress response element, anaerobic induction, and MYB binding site play a dominant role in drought responsiveness. Additionally, expression pattern analysis revealed variations in the expression of ginger TCP gene among different tissues and in response to diverse abiotic stresses (drought, low temperature, heat, and salt). Our research offers a thorough examination of TCP members within the ginger plant. This analysis greatly contributes to the understanding of how TCP genes regulate tissue development and response to stress, opening up new avenues for further exploration in this field.
RESUMEN
Multi-drug resistance (MDR) remains the main culprit for the low survival rate of advanced colorectal cancer (CRC). Photothermal-therapy (PPT) is effective to kill MDR tumor cells, but fails to completely eradicate tumors. In this study, we prepared a nanocomposite based on gold nanorod core with triple layer coating (GNRs/mSiO2/PHIS/TPGS/DOX) to combat multidrug resistant (MDR) colorectal cancer via multi-strategies. We first synthesized the mesoporous silica-coated gold nanorods (GNRs/mSiO2), and loaded with antitumor drug doxorubicin (DOX) to realize a combination of chemo- and photothermal-therapy. To reverse DOX resistance, pH responsive poly-histidine (PHIS) was conjugated on GNRs/mSiO2 to increase drug intracellular accumulation via efficient endo/lysosome escape; d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was then assembled on the surface of the particles to realize drug intracellular retention by inhibition P-glycoprotein. The results showed that the nanocomposite exhibited a highly efficient photothermal conversion in the NIR region, a pH and NIR triggered drug release profile and an increment of DOX intracellular accumulation and cytotoxicity on MDR SW620/Ad300â¯cells. Most importantly, the nanocomposite showed the most potent antitumor efficacy without obvious systemic toxicity comparing to other control groups with either chemo- or photothermal therapy alone on SW620/Ad300 tumor bearing mice. Altogether, the successful preparation of the nanocomposite and its potent efficacy might provide evidence for the future design and develop of nano-therapeutic system in the treatment of MDR colorectal cancer.
Asunto(s)
Portadores de Fármacos/química , Resistencia a Antineoplásicos , Oro/química , Nanocompuestos/química , Nanotubos/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Histidina/química , Humanos , Rayos Infrarrojos , Masculino , Ratones , Ratones Desnudos , Fototerapia , Dióxido de Silicio/química , Vitamina E/químicaRESUMEN
BACKGROUND: Local photothermal therapy (PTT) provides an easily applicable, noninvasive adjunctive therapy for colorectal cancer (CRC), especially when multidrug resistance (MDR) occurs. However, using PTT alone does not result in complete tumor ablation in many cases, thus resulting in tumor recurrence and metastasis. MATERIALS AND METHODS: In this study, we aim to develop a personalized local therapeutic platform combining PTT with long-acting chemotherapy for the treatment of MDR CRC. The platform consists of polyethylene glycol (PEG)-coated gold nanorods (PEG-GNRs) and D-alpha-tocopheryl PEG 1000 succinate (TPGS)-coated paclitaxel (PTX) nanocrystals (TPGS-PTX NC), followed by the incorporation into an in situ hydrogel (gel) system (GNRs-TPGS-PTX NC-gel) before injection. After administration, PEG-GNRs can exert quick and efficient local photothermal response under near-infrared laser irradiation to shrink tumor; TPGS-PTX NC then provides a long-acting chemotherapy due to the sustained release of PTX along with the P-glycoprotein inhibitor TPGS to reverse the drug resistance. RESULTS: The cytotoxicity studies showed that the IC50 of GNRs-TPGS-PTX NC-gel with laser irradiation decreased to ~178-folds compared with PTX alone in drug-resistant SW620 AD300 cells. In the in vivo efficacy test, after laser irradiation, the GNRs-TPGS-PTX NC-gel showed similar tumor volume inhibition compared with GNRs-gel at the beginning. However, after 14 days, the tumor volume of the mice treated with GNRs-gel quickly increased, while that of the mice treated with GNRs-TPGS-PTX NC-gel remained controllable due to the long-term chemotherapeutic effect of TPGS-PTX NC. The mice treated with GNRs-TPGS-PTX NC-gel also showed no weight loss and obvious organ damages and lesions during the treatment, indicating a low systemic side effect profile and a good biocompatibility. CONCLUSION: Overall, the nano-complex may serve as a promising local therapeutic patch against MDR CRC with one-time dosing to achieve a long-term tumor control. The doses of PEG-GNRs and TPGS-PTX NC can be easily adjusted before use according to patient-specific characteristics potentially making it a personalized therapeutic platform.