Lectin drug conjugate therapy for colorectal cancer.
Lectin drug conjugate therapy for colorectal cancer.
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DOI：
10.1111/cas.14687
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发表时间：
2020-12
期刊：
影响因子：
5.7
通讯作者：
Tateno H
中科院分区：
文献类型：
--
作者：
Kitaguchi D;Oda T;Enomoto T;Ohara Y;Owada Y;Akashi Y;Furuta T;Yu Y;Kimura S;Kuroda Y;Kurimori K;Miyazaki Y;Furuya K;Shimomura O;Tateno H
耐药性是结直肠癌（CRC）治疗的一个障碍，因为它与预后不良有关。rBC 2LCN是从伯克霍尔德氏菌分离的凝集素，其结合具有岩藻糖部分的细胞表面聚糖。由于岩藻糖基化在许多类型的癌症中增强，如果CRC细胞特异性地呈现这样的聚糖，则这种凝集素可以是有效的药物载体。因此，我们检查了凝集素药物缀合物疗法在CRC小鼠异种移植模型中的治疗功效和毒性。在体外评估rBC 2LCN对人CRC细胞系HT-29、LoVo、LS 174 T和DLD-1的亲和力。通过MTT测定评价凝集素药物缀合物，假单胞菌外毒素A（PE 38）的rBC 2LCN-38 kDa结构域的杀细胞功效。在干预组和对照组之间比较每个CRC细胞系衍生的小鼠异种移植模型的治疗效果和毒性。LS 174 T和DLD-1细胞系显示出对rBC 2LCN的强亲和力。在异种移植模型中，与单独使用对照治疗相比，rBC 2LCN-PE 38组中的肿瘤体积显著减小。然而，HT-29细胞系显示出弱亲和力和差的治疗效果。未观察到显著毒性或不良反应。总之，我们证明了rBC 2LCN凝集素结合CRC细胞，并且rBC 2LCN-PE 38在体内显著抑制肿瘤生长。此外，药物缀合物的功效与其对每个CRC细胞系的结合亲和力相关。这些结果表明，凝集素药物缀合物疗法具有作为CRC细胞表面聚糖的新型靶向疗法的潜力。rBC 2LCN凝集素对结直肠癌（CRC）细胞表面具有亲和力。rBC 2LCN-PE 38在小鼠模型中抑制皮下CRC肿瘤生长速率。凝集素药物偶联物治疗可能成为结直肠癌的一种新的治疗选择。
Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT‐29, LoVo, LS174T, and DLD‐1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN‐38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line‐derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD‐1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN‐PE38 group was significantly reduced compared with that using control treatment alone. However, the HT‐29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN‐PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans. rBC2LCN lectin showed affinity for colorectal cancer (CRC) cell surface. rBC2LCN‐PE38 suppressed subcutaneous CRC tumor growth rates in mouse models. Lectin drug conjugate therapy could be a novel therapeutic option for CRC.
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影响因子：
4.6
作者：
Saito S;Hiemori K;Kiyoi K;Tateno H
通讯作者：
Tateno H
影响因子：
8.8
作者：
Hirakawa, M.;Takimoto, R.;Tamura, F.;Yoshida, M.;Ono, M.;Murase, K.;Sato, Y.;Osuga, T.;Sato, T.;Iyama, S.;Miyanishi, K.;Takada, K.;Hayashi, T.;Kobune, M.;Kato, J.
通讯作者：
Kato, J.
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
DOI：
10.1073/pnas.0402088101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Koike, T;Kimura, N;Kanangi, R
通讯作者：
Kanangi, R
影响因子：
56.9
作者：
KOPROWSKI, H;HERLYN, M;SEARS, HF
通讯作者：
SEARS, HF