Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity.
Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity.
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DOI：
10.18632/oncotarget.2369
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发表时间：
2014-09-30
期刊：
影响因子：
--
通讯作者：
Hoffman RM
中科院分区：
文献类型：
--
作者：
Yano S;Li S;Han Q;Tan Y;Bouvet M;Fujiwara T;Hoffman RM
肿瘤对化疗的反应的主要障碍是肿瘤内的绝大多数癌细胞在G 0/G1中是静止的，其中癌细胞对化疗具有抗性。为了试图解决肿瘤中静止细胞的问题，用重组甲硫氨酸酶（rMET酶）处理癌细胞，其选择性地将癌细胞捕获在S/G2中。用荧光泛素化细胞周期指示剂（FUCCI）可视化癌细胞的细胞周期阶段。在通过FUCCI成像通过癌细胞的绿色荧光鉴定的rMET酶诱导的S/G2期阻断时，给予癌细胞S/G2依赖性化疗药物，其与DNA相互作用或阻断DNA合成，如阿霉素、顺铂或5-氟尿嘧啶。仅用药物治疗癌细胞，而没有rMET酶诱导的S/G2期阻断，导致大多数癌细胞群体被阻断在G 0/G1期，通过癌细胞在FUCCI系统中变成红色荧光来鉴定。G 0/G1期阻滞的细胞对化疗产生耐药性。相比之下，通过rMETase治疗将癌细胞捕获在S/G2期，然后进行FUCCI成像引导的化疗，在杀死癌细胞方面非常有效。
A major impediment to the response of tumors to chemotherapy is that the large majority of cancer cells within a tumor are quiescent in G0/G1, where cancer cells are resistant to chemotherapy. To attempt to solve this problem of quiescent cells in a tumor, cancer cells were treated with recombinant methioninase (rMETase), which selectively traps cancer cells in S/G2. The cell cycle phase of the cancer cells was visualized with the fluorescence ubiquitination cell cycle indicator (FUCCI). At the time of rMETase-induced S/G2-phase blockage, identified by the cancer cells' green fluorescence by FUCCI imaging, the cancer cells were administered S/G2-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil. Treatment of cancer cells with drugs only, without rMETase-induced S/G2 phase blockage, led to the majority of the cancer-cell population being blocked in G0/G1 phase, identified by the cancer cells becoming red fluorescent in the FUCCI system. The G0/G1 blocked cells were resistant to the chemotherapy. In contrast, trapping of cancer cells in S/G2 phase by rMETase treatment followed by FUCCI-imaging-guided chemotherapy was highly effective in killing the cancer cells.
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DOI：
10.1073/pnas.76.3.1313
发表时间：
1979-01-01
影响因子：
11.1
作者：
HOFFMAN, RM;JACOBSEN, SJ;ERBE, RW
通讯作者：
ERBE, RW
影响因子：
4.3
作者：
Blagosklonny, MV
通讯作者：
Blagosklonny, MV
DOI：
10.1111/j.1349-7006.1995.tb03082.x
发表时间：
1995-05-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
GOSEKI, N;YAMAZAKI, S;TAKAHASHI, H
通讯作者：
TAKAHASHI, H
DOI：
10.1073/pnas.79.14.4248
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
COALSON, DW;MECHAM, JO;HOFFMAN, RM
通讯作者：
HOFFMAN, RM
DOI：
10.1073/pnas.77.12.7306
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HOFFMAN, RM;JACOBSEN, SJ
通讯作者：
JACOBSEN, SJ